Xenobiotic-Metabolizing Cytochrome P450 Enzymes in the Human Feto-Placental Unit: Role in Intrauterine Toxicity

References

• Mihaly, G. W. and Morgan, D. J., Placental drug transfer: effect of gestational age and species, Pharmacol. Ther., 23, 253–266, 1984.
   Web of Science ®Google Scholar
• Ward, R. M., Drug therapy of the fetus, J. Clin. Pharmacol., 33, 780–789, 1993.
   PubMed Web of Science ®Google Scholar
• Wells, P. G. and Winn, L. M., Biochemical toxicology of chemical teratogenesis, Crit. Rev. Biochem. Mol. Biol., 31, 1–40, 1996.
   PubMed Web of Science ®Google Scholar
• Juchau, M. R., Lee, Q. P., and Fantel, A. G., Xenobiotic biotransformation/bioactivation in organogenesis-stage conceptal tissues: implications for embryotoxicity and teratogenesis, Drug Metab. Rev., 24, 195–238, 1992.
   PubMed Web of Science ®Google Scholar
• Farrar, H. C. and Blumer, J. L., Fetal effects of maternal drug exposure, Annu. Rev. Pharmacol. Toxicol., 31, 525–547, 1991.
   PubMed Web of Science ®Google Scholar
• Peters, P. W. J., Garbis-Berkvens, H. M., and Bannigan, J. G., Drugs of choice in pregnancy: primary prevention of birth defects, Re-prod. Toxicol., 7, 399–404, 1993.
   PubMed Web of Science ®Google Scholar
• Kuss, E., The fetoplacental unit of primates, Exp. Clin. Endocrinol., 102, 135–165, 1994.
   PubMedGoogle Scholar
• Guengerich, F. P., Bioactivation and detoxica-tion of toxic and carcinogenic chemicals, Drug Metab. Dispos., 21, 1–6, 1993.
   PubMed Web of Science ®Google Scholar
• Gonzalez, F. J. and Gelboin, H. V., Role of human cytochromes P450 in the metabolic activation of chemical carcinogens and toxins, Drug Metab. Rev., 26, 165–183, 1994.
   PubMed Web of Science ®Google Scholar
• Hinson, J. A. and Forkert, P.-G., Phase II enzymes and bioactivation, Can. J. Physiol. Pharmacol., 73, 1407–1413, 1995.
   PubMed Web of Science ®Google Scholar
• Raucy, J. L. and Carpenter, S. J., The expression of xenobiotic-metabolizing cyto-chromes P450 in fetal tissues, J. Pharmacol. Toxicol. Meth., 29, 121–128, 1993.
   PubMed Web of Science ®Google Scholar
• Pasanen, M. and Pelkonen, O., The expression and environmental regulation of P450 enzymes in human placenta, Crit. Rev. Toxicol., 24, 211–229, 1994.
   PubMed Web of Science ®Google Scholar
• Gonzalez, F. J. and Gelboin, H. V., Human cytochromes P450: evolution and cDNA-di-rected expression, Environ. Health Perspect., 98, 81–85, 1992.
   PubMed Web of Science ®Google Scholar
• Wrighton, S. A. and Stevens, J. C., The human hepatic cytochromes P450 involved in drug metabolism, Crit. Rev. Toxicol., 22, 1–21, 1992.
   PubMed Web of Science ®Google Scholar
• Nelson, D. R., Koymans, L., Kamataki, T., Stegeman, J. J., Feyereisen, R., Waxman, D. J., Waterman, M. R., Gotoh, O., Coon, M. J., Estabrook, R. W., Gunsalus, I. C., and Nebert, D. W., P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature, Pharmacogenet-ics, 6, 1–42, 1996.
   PubMedGoogle Scholar
• Gonzalez, F. J., Human cytochromes P450: problems and prospects, Trends Pharmacol. Sci., 13, 346–352, 1992.
   PubMed Web of Science ®Google Scholar
• Raunio, H., Pasanen, M., Mäenpää, J., Hakkola, J., and Pelkonen, O., Expression of extrahepatic cytochrome P450 in humans, in Advances in Drug Metabolism in Man, Pacifici, G. M. and Fracchia, G.N., Eds., European Commission, Office for Official Publications of the European Communities, Luxembourg, 1995, 234.
   Google Scholar
• Ioannides, C. and Parke, D. V., Induction of cytochrome P4501 as an indicator of potential chemical carcinogenesis, Drug Metab. Rev., 25, 485–501, 1993.
   PubMed Web of Science ®Google Scholar
• Nebert, D. W., Drug-metabolizing enzymesin ligand-modulated transcription, Biochem. Pharmacol., 47, 25–37, 1994.
   PubMed Web of Science ®Google Scholar
• Beresford, A. P., CYP1A1: friend of foe, Drug Metab. Rev., 25, 503–517, 1993.
   PubMed Web of Science ®Google Scholar
• Kawajiri, K., Nakachi, K., Imai, K., Watanabe, J., and Hayashi, S., The CYP1A1 gene and cancer susceptibility, Crit. Rev. Oncol. Hematol., 14, 77–87, 1993.
   PubMed Web of Science ®Google Scholar
• Zhang, Z.-Y., Fasco, M. J., Huang, L., Guengerich, F. P., and Kaminsky, L. S., Characterization of purified human recombinant cytochrome P4501A1-Ile462 and -Val462: assessment of a role for the rare allele in carcinogenesis, Cancer Res., 56, 3926–3933, 1996.
   PubMed Web of Science ®Google Scholar
• Persson, I., Johansson, I., and Ingelman-Sundberg, M., In vitro kinetics of two human CYP1A1 variant enzymes suggested to be associated with interindividual differences in cancer susceptibility, Biochem. Biophys. Res. Commun., 231, 227–230, 1997.
   PubMed Web of Science ®Google Scholar
• Sengstag, C., Eugster, H.-P., and Würgler, F. E., High promutagen activating capacity of yeast microsomes containing human cyto-chrome P-450 1A and human NADPH-cyto-chrome P-450 reductase, Carcinogenesis, 15, 837–843, 1994.
   PubMed Web of Science ®Google Scholar
• Pelkonen, O. and Breimer, D. D., Role of environmental factors in the pharmacokinet-ics of drugs—considerations with respect to animal models, in Handbook of Experimental Pharmacology, Welling, P. G. and Balant, L. P., Eds., Karger, Basel, 1994, 289.
   Google Scholar
• Nebert, D. W., The Ah locus: genetic differences in toxicity, cancer, mutation, and birth defects, Crit. Rev. Toxicol., 20, 137–152, 1989.
   PubMed Web of Science ®Google Scholar
• Idle, J. R., Armstrong, M., Boddy, A. V., Boustead, C., Cholerton, S., Cooper, J., Daly, A. K., Ellis, J., Gregory, W., Hadidi, H., Höfer, C., Holt, J., Leathart, J., McCracken, N., Monkman, S. C., Painter, J. E., Taber, H., Walker, D., and Yule, M., The pharmacogenetics of chemical carcino-genesis, Pharmacogenetics, 2, 246–258, 1992.
   PubMedGoogle Scholar
• Raunio, H., Husgafvel-Pursiainen, K., Anttila, S., Hietanen, E., Hirvonen, A., andPelkonen, O., Diagnosis of polymorphismsin carcinogen-activating and inactivating enzymes and cancer susceptibility—review, Gene, 159, 113–121, 1995.
   PubMed Web of Science ®Google Scholar
• Nebert, D. W., McKinnon, R. A., and Puga, A., Human drug-metabolizing enzyme polymorphisms: effects on risk of toxicity and cancer, DNA Cell Biol., 15, 273–280, 1996.
   PubMed Web of Science ®Google Scholar
• Farin, F. M., Pohlman, T. H., and Omiecinski, C. J., Expression of cytochrome P450s and microsomal epoxide hydrolase in primary cultures of human umbilical vein endothelial cells, Toxicol. Appl. Pharmacol., 124, 1–9, 1994.
   PubMed Web of Science ®Google Scholar
• Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., and Guengerich, F. P., Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians, J. Pharmacol. Exp. Ther., 270, 414–423, 1994.
   PubMed Web of Science ®Google Scholar
• Guengerich, F. P., Cytochromes P450 of human liver. Classification and activity profiles of the major enzymes, in Advances in Drug Metabolism in Man, Pacifici, G. M., and Fracchia, G. N., Eds., European Commission. Office for the Official Publications of the European Communities, Luxenbourg, 1995, 179.
   Google Scholar
• Eaton, D. L., Gallagher, E. P., Bammler, T. K., and Kunze, K. L., Role of cytochrome P450IA2 in chemical carcinogenesis: implications for human variability in expression and enzyme activity, Pharmacogenetics, 5, 259– 274, 1995.
   PubMedGoogle Scholar
• Butler, M. A., Iwasaki, M., Guengerich, F. P., and Kadlubar, F. F., Human cyto-chrome P-450PA (P-450IA2), the phenacetin O-deetylase, is primarily reponsible for hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines, Proc. Natl. Acad. Sci. USA, 86, 7696–7700, 1989.
   PubMed Web of Science ®Google Scholar
• Guengerich, F. P., Catalytic selectivity of human cytochrome P450 enzymes: relevance to drug metabolism and toxicity, Toxicol. Lett., 70, 133–138, 1994.
   PubMed Web of Science ®Google Scholar
• Sutter, T. R., Tang, Y. M., Hayes, C. L., Wo, Y.-Y.P., Jabs, E. W., Li, X., Yin, H., Cody, C. W., and Greenlee, W. F., Complete cDNA sequence of a human dioxin-in-ducible mRNA identifies a new gene subfamily of a cytochrome that maps to chromosome 2, J. Biol. Chem., 269, 13092–13099, 1994.
   PubMed Web of Science ®Google Scholar
• Shimada, T., Hayes, C. L., Yamazaki, H., Amin, S., Hecht, S. S., Guengerich, F. P.,and Sutter, T. R., Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1, Cancer Res., 56, 2979–2984, 1996.
   PubMed Web of Science ®Google Scholar
• Hakkola, J., Pasanen, M., Pelkonen, O., Hukkanen, J., Evisalmi, S., Anttila, S., Rane, A., Mäntylä, M., Purkunen, R., Saarikoski, S., Tooming, M., and Raunio, H., Expression of CYP1B1 in human adult and fetal tissues and differential inducibility of CYP1B1 and CYP1A1 by Ah receptor ligands in human placenta and cultured cells. Carcinogenesis, 18, 391–397, 1997.
   PubMed Web of Science ®Google Scholar
• Spink, D. C., Hayes, C. L., Young, N. R., Christou, M., Sutter, T. R., Jefcoate, C. R., and Gierthy, J. F., The effect of 2,3,7,8-tetra-chlorodibenzo-p-dioxin on estrogen metabolism in MCF-7 breast cancer cells: evidence for induction of a novel 17b-estradiol 4-hy-droxylase, J. Steroid Biochem. Mol. Biol., 51, 251–258, 1994.
   PubMed Web of Science ®Google Scholar
• Liehr, J. G., Ricci, M. J., Jefcoate, C. R., Hannigan, E. V., Hokanson, J. A., and Zhu, B. T., 4-Hydroxylation of estradiol by human uterine myometrium and myoma microsomes: implications for the mechanism of uterine tu-morigenesis, Proc. Natl. Acad. Sci. USA, 92, 9220–9224, 1995.
   PubMed Web of Science ®Google Scholar
• Savas, Ü., Bhattacharyya, K. K., Christou, M., Alexander, D. L., and Jefcoate, C. R.,Mouse cytochrome P-450EF, representative of a new 1B subfamily of cytochrome P-450s, J. Biol. Chem., 269, 14905–14911, 1994.
   PubMed Web of Science ®Google Scholar
• Martucci, C. P. and Fishman, J., P450 enzymes of estrogen metabolism, Pharmac. Ther., 57, 237–257, 1993.
   PubMed Web of Science ®Google Scholar
• Hoffman, S. M. G., Fernandez-Salguero, P., Gonzalez, F. J., and Mohrenweiser, H. W.,Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19, J. Mol. Evolut., 41, 894–900, 1995.
   PubMed Web of Science ®Google Scholar
• Fernandez-Salguero, P., Hoffman, S. M. G., Cholerton, S., Mohrenweiser, H., Raunio, H., Rautio, A., Pelkonen, O., Huang, J., Evans, W. E., Idle, J. R., and Gonzalez, F. J., A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2Agenes and identification of variant CYP2A6alleles, Am. J. Hum. Genet., 57, 651–660, 1995.
   PubMed Web of Science ®Google Scholar
• Ding, S., Lake, B. G., Friedberg, T., and Wolf, C. R., Expression and alternative splicing of the cytochrome P-450 CYP2A7, Biochem. J. 306, 161–166, 1995.
   PubMed Web of Science ®Google Scholar
• Raunio, H., Syngelmä, T., Pasanen, M., Juvonen, R., Honkakoski, P., Kairaluoma, M. A., Sotaniemi, E. A., Lang, M. A., and Pelkonen, O., Immunochemical and catalyti-cal studies on hepatic coumarin 7-hydroxylase in man, rat, and mouse, Biochem. Pharmacol., 37, 3889–3895, 1988.
   PubMed Web of Science ®Google Scholar
• Fernandez-Salguero, P. and Gonzalez, F. J., The CYP2A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis, Pharmacogenetics, 5, S123–S128, 1995.
   PubMedGoogle Scholar
• Rautio, A., Kraul, H., Kojo, A., Salmela, E., and Pelkonen, O., Interindividual variability of coumarin 7-hydroxylation in healthy individuals, Pharmacogenetics, 2, 227–233, 1992.
   PubMedGoogle Scholar
• Cholerton, S., Idle, M. E., Vas, A., Gonzalez, F. J., and Idle, J. R., Comparison of a novel thin-layer chromatographic-fluorescence detection method with a spectrofluorometric method for the determination of 7-hydroxycou-marin in human urine, J. Chromatogr. 575, 325–330, 1992.
   PubMed Web of Science ®Google Scholar
• Imaoka, S., Yamada, T., Hiroi, T., Hayashi, K., Sakaki, T., Yabusaki, Y., and Funae, Y., Multiple forms of human P450 expressed in Saccharomyces cerevisiae, systematic characterization and comparison with those of the rat, Biochem. Pharmacol., 51, 1041–1050, 1996.
   PubMed Web of Science ®Google Scholar
• Waxman, D. J., Lapenson, D. P., Aoyama, T., Gelboin, H. V., Gonzalez, F. J., and Korzekwa, K., Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s, Arch. Biochem. Biophys. 290, 160–166, 1991.
   PubMed Web of Science ®Google Scholar
• Goldstein, J. A. and de Morais, S. M. F., Biochemistry and molecular biology of the human CYP2C subfamily, Pharmacogenetics, 4, 285–299, 1994.
   PubMedGoogle Scholar
• Stubbins, M. J., Harries, L. W., Smith, G., Tarbit, M. H., and Wolf, C. R., Genetic analysis of the human cytochrome P450 CYP2C9 locus, Pharmacogenetics, 6, 429–439, 1996.
   PubMedGoogle Scholar
• Morel, F., Beaune, P. H., Ratanasavanh, D., Flinois, J.-P., Yang, C. S., Guengerich, F. P., and Guillouzo, A., Expression of cytochrome P-450 enzymes in cultured human hepatocytes, Eur. J. Biochem. 191. 437–444, 1990.
   PubMedGoogle Scholar
• Leo, M. A., Lasker, J. M., Raucy, J. L., Kim, C.-I., Black, M., and Lieber,. S.,Metabolism of retinol and retinoic acids by human liver cytochrome P450IIC8, Arch. Bio-chem. Biophys., 269, 305–312, 1989.
   PubMed Web of Science ®Google Scholar
• Cholerton, S., Daly, A. K., and Idle, J. R., The role of individual human cytochromes P450 in drug metabolism and clinical response, Trends Pharmacol. Sci., 13, 434–439, 1992.
   PubMed Web of Science ®Google Scholar
• Heim, M. H. and Meyer, U. A., Evolution of a highly polymorphic human cytochrome P450 gene cluster: CYP2D6, Genomics, 14, 49–58, 1992.
   PubMed Web of Science ®Google Scholar
• Ingelman-Sundberg, M. and Johansson, I., The molecular genetics of the human drug metabolizing cytochrome P450s, in Advances in Drug Metabolism in Man, Pacifici, G. M. and Fracchia, G. N. Eds., Office for Official Publications of the European Communities, Luxemburg, 1995, 534.
   Google Scholar
• Song, B.-J., Gelboin, H. V., Park, S.-S., Yang, C. S., and Gonzalez, F. J., Complementary DNA and protein sequences of ethanol-induci-ble rat and human cytochrome P-450s, J. Biol. Chem., 261, 16689–16697, 1986.
   PubMed Web of Science ®Google Scholar
• Ronis, M. J. J., Lindros, K. O., and Ingelman-Sundberg, M., The CYP2E subfamily, in Cy-tochromes P450. Metabolic and Toxicological Aspects, Ioannides, C. and Parke, D. V., Eds., CRC Press, Boca Raton, 1996, 211.
   Google Scholar
• Koop, D. R. Oxidative and reductive metabolism by cytochrome P450 2E1, FASEB J., 6, 724–730, 1992.
   PubMed Web of Science ®Google Scholar
• Patten, C., Thomas, P. E., Guy, R., Lee, M., Gonzalez, F. J., Guengerich, F. P., and Yang, C. S., Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics, Chem. Res. Toxicol., 6, 511–518, 1993.
   PubMed Web of Science ®Google Scholar
• Peter, R., Böcker, R. G., Beaune, P. H., Iwasaki, M., Guengerich, F. P., and Yang, C.-S., Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450 IIE1, Chem. Res. Toxicol., 3, 566–573, 1990.
   PubMed Web of Science ®Google Scholar
• Nhamburo, P. T., Kimura, S., McBride, O. W., Kozak, C. A., Gelboin, H. V., and Gonzalez, F. J., The human CYP2F gene family: identification of a cDNA encoding a new cytochrome P450, cDNA-directed expression, and chromosome mapping, Biochemistry, 29, 5491–5499, 1990.
   PubMed Web of Science ®Google Scholar
• Thornton-Manning, J. R., Ruangyuttikarn, W., Gonzalez, F. J., and Yost, G. S., Metabolic activation of the pneumotoxin, 3-meth-ylindole, by vaccinia-expressed cytochrome P450s, Biochem. Biophys. Res. Commun., 181, 100–107, 1991.
   PubMed Web of Science ®Google Scholar
• Wu, S., Moomaw, C. R., Tomer, K. B., Falck, J. R., and Zeldin, D. C., Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart, J. Biol. Chem., 271, 3460– 3468, 1996.
   PubMed Web of Science ®Google Scholar
• Yamazaki, H., Inui, Y., Wrighton, S. A., Guengerich, F. P., and Shimada, T., Pro-carcinogen activation by cytochrome P450 3A4 and 3A5 expressed in Escherichia coli and by human liver microsomes, Carcino-genesis, 16, 2167–2170, 1995.
   PubMed Web of Science ®Google Scholar
• Watkins, P. B., Wrighton, S. A., Maurel, P., Schuetz, E. G., Mendez-Picon, G., Parker, G. A., and Guzelian, P. S., Identification of an inducible form of cytochrome P-450 in human liver, Proc. Natl. Acad. Sci. USA, 82, 6310–6314, 1985.
   PubMed Web of Science ®Google Scholar
• Neuvonen, P. J., Interactions in first-pass metabolism and variability in drug response, in Clinical Measurement in Drug Evaluation, Nimmo, W. S. and Tucker, G. T. Eds., John Wiley & Sons Ltd, 1995, 301.
   Google Scholar
• Kolars, J. C., Lown, K. S., Schmiedlin-Ren, P., Ghosh, M., Fang, C., Wrighton, S. A., Merion, R. M., and Watkins, P. B., CYP3A gene expression in human gut epithelium, Phar-macogenetics, 4, 247–259, 1994.
   PubMedGoogle Scholar
• Aoyama, T., Yamano, S., Waxman, D. J., Lapenson, D. P., Meyer, U. A., Fischer, V., Tyndale, R., Inaba, T., Kalow, W., Gelboin, H. V., and Gonzalez, F. J., Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver, J. Biol. Chem., 264, 10388–10395, 1989.
   PubMed Web of Science ®Google Scholar
• Wrighton, S. A., Ring, B. J., Watkins, P. B., and VandenBranden, M., Identification of apolymorphically expressed member of the hu– man cytochrome P-450III family, Mol. Pharmacol., 86, 97–05, 1989.
   Google Scholar
• Wrighton, S. A., Brian, W. R., Sari, M. A., Iwasaki, M., Guengerich, F. P., Raucy, J. L., Molowa, D. T., and VandenBranden, M.,Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3), Mol. Pharmacol., 38, 207–213, 1990.
   PubMed Web of Science ®Google Scholar
• Schuetz, E. G., Schuetz, J. D., Grogan, W. M., Naray-Fejes-Toth, A., Fejes-Toth, G., Raucy, J., Guzelian, P., Gionela, K., and Watlington, C.O., Expression of cyto-chrome P450 3A in amphibian, rat, and human kidney, Arch. Biochem. Biophys., 294, 206– 214, 1992.
   PubMed Web of Science ®Google Scholar
• Kivistö, K. T., Griese, E.-U., Fritz, P., Linder, A., Hakkola, J., Raunio, H., Beaune, P., and Kroemer, H. K., Expression of cyto-chrome P4503A enzymes in human lung: a combined RT-PCR and immunohistochemi-cal analysis of normal tissue and lung tumors, Naunyn-Schmiedeberg Arch. Pharmacol., 353, 207–212, 1996.
   PubMed Web of Science ®Google Scholar
• Kitada, M., Kamataki, T., Itahashi, K., Rikihisa, T., Kato, R., and Kanakubo, Y.,Purification and properties of cytochrome P-450 from homogenates of human fetal livers, Arch. Biochem. Biophys., 241, 275–280, 1985.
   PubMed Web of Science ®Google Scholar
• Kitada, M. and Kamataki, T. Cytochrome P450 in human fetal liver: significance and fetal specific expression, Drug Metab. Rev., 26, 305– 323, 1994.
   PubMed Web of Science ®Google Scholar
• Komori, M., Nishio, K., Kitada, M., Shiramatsu, K., Muroya, K., Soma, M., Nagashima, K., and Kamataki, T., Fetus-specific expression of a form of cytochrome P-450 in human livers, Biochemistry, 29, 4430– 4433, 1990.
   PubMed Web of Science ®Google Scholar
• Schuetz, J. D., Beach, D. L., and Guzelian, P. S., Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver, Pharmacogenetics, 4, 11–20, 1994.
   PubMedGoogle Scholar
• Hakkola, J., Pasanen, M., Purkunen, R., Saarikoski, S., Pelkonen, O., Mäenpää, J., Rane, A., and Raunio, H., Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver, Biochem. Pharmacol., 48, 59–64, 1994.
   PubMed Web of Science ®Google Scholar
• Greuet, J., Pichard, L., Bonfils, C., Domergue, J., and Maurel, P., The fetal specific gene CYP3A7 is inducible by rifampicin in adult human hepatocytes in primary culture, Biochem. Biophys. Res. Commun., 225, 689–694, 1996.
   PubMed Web of Science ®Google Scholar
• Kitada, M., Kamataki, T., Itahashi, K., Rikihisa, T., and Kanakubo, Y., Significance of cytochrome P-450 (P-450 HFLa) of human fetal livers in the steroid and drug oxidations, Biochem. Pharmacol., 36, 453–456, 1987.
   PubMed Web of Science ®Google Scholar
• Nhamburo, P. T., Gonzalez, F. J., McBride, O. W., Gelboin, H. V., and Kimura, S.,Identification of a new P450 expressed in human lung: complete cDNA sequence, cDNA-directed expression, and chromosome mapping, Biochemistry, 28, 8060–8066, 1989.
   PubMed Web of Science ®Google Scholar
• 84.Yokotani, N., Sogawa, K., Matsubara, S., Gotoh, O., Kusunose, E., Kusunose, M., and Fujii-Kuriyama, Y., cDNA cloning of cytochrome P-450 related to P-450p-2 from the cDNA library of human placenta: gene structure and expression, Eur. J. Biochem., 187, 23– 29, 1990.
   PubMedGoogle Scholar
• McKinnon, R. A., Burgess, W. M., Gonzalez, F. J., Gasser, R., and McManus, M. E., Species-specific expression of CYP4B1 in rabbit and human gastrointestinal tissues, Pharmaco-genetics, 4, 260–270, 1994.
   PubMedGoogle Scholar
• Denison, M. S. and Whitlock, J. P. J., Xe-nobiotic-inducible transcription of cytochrome P450 genes, J. Biol. Chem., 270, 18175–18178, 1995.
   PubMed Web of Science ®Google Scholar
• Chen, D., Lepard, G., and Kemper, B., A transcriptional regulatory element common to a large family of hepatic cytochrome P450 genes is a functional binding site of the orphan receptor HNF-4, J. Biol. Chem., 269, 5420–5427, 1994.
   PubMed Web of Science ®Google Scholar
• 88.Gonzalez, F. J., Liu, S.-Y., and Yano, M., Regulation of cytochrome P450 genes: molecular mechanisms, Pharmacogenetics, 3, 51– 57, 1993.
   PubMedGoogle Scholar
• Okey, A. B., Enzyme induction in the cyto-chrome P-450 system, Pharmacol. Ther., 45, 241–298, 1990.
   PubMed Web of Science ®Google Scholar
• Hankinson, O., The aryl hydrocarbon receptor complex, Annu. Rev. Pharmacol. Toxicol., 35, 307–340, 1995.
   PubMed Web of Science ®Google Scholar
• Pohjanvirta, R. and Tuomisto, J., Short-term toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in laboratory animals: effects, mechanisms, and animal models, Pharmacol. Rev. 46, 483–549, 1994.
   PubMed Web of Science ®Google Scholar
• Okey, A. B., Riddick, D. S., and Harper, P. A., The Ah receptor: mediator of the tox-icity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds, Toxicol. Lettt., 70. 1–22, 1994.
   PubMed Web of Science ®Google Scholar
• Peters, J. M. and Wiley, L. M., Evidence that murine preimplantation embryos express aryl hydrocarbon receptor, Toxicol. Appl. Pharmacol., 134, 214–221, 1995.
   PubMed Web of Science ®Google Scholar
• Fernandez-Salguero, P., Pineau, T., Hilbert, D. M., McPhail, T., Lee, S. S. T., Kimura, S., Nebert, D. W., Rudikoff, S., Ward, J. M., and Gonzalez, F. J., Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor, Science, 268, 722– 726, 1995.
   PubMed Web of Science ®Google Scholar
• Schmidt, J. V., Su, G. H.-T., Reddy, J. K., Simon, M. C., and Bradfield, C. A., Characterization of a murine Ahr null allele: animal model for the toxicity of halogenated dioxins and biphenyls, Proc. Natl. Acad. Sci. USA, 93, 6731–6736, 1996.
   PubMed Web of Science ®Google Scholar
• Waxman, D. J. and Azaroff, L., Phenobarbital induction of cytochrome P-450 gene expression, Biochem. J., 281, 577–592, 1992.
   PubMed Web of Science ®Google Scholar
• Lake, B. G. Peroxisome proliferation: current mechanisms relating to non-genotoxic carci-nogenesis, Toxicol. Lettt., 82/83, 673–681, 1995.
   Google Scholar
• Schuetz, J. D., Schuetz, E. G., Thottassery, J. V., Guzelian, P. S., Strom, S., and Sun, D.,Identification of a novel dexamethasone responsive enhancer in the human CYP3A5 gene and its activation in human and rat liver cells, Mol. Pharmacol., 49, 63–72, 1996.
   PubMed Web of Science ®Google Scholar
• Ingelman-Sundberg, M., Ethanol-induciblecytochrome P450 2E1. Regulation, radical formation and toxicological importance, in FreeRadicals: From Basic Science to Medicine, Poli, G., Albano, E., and Dianzani, M. U., Eds., Birkhäuser, Basel, 1993, 287.
   Google Scholar
• Lieber, C. S., Alcohol and the liver: 1994 update, Gastroenterology, 106, 1085–1105, 1994.
   Google Scholar
• Whyatt, R. M. and Perera, F. P., Application of biologic markers to studies of environmen-tal risks in children and the developing fetus, Environ. Health Perspect., 103(Suppl. 6), 105– 110, 1995.
   Google Scholar
• Pelkonen, O., Biotransformation of xenobi-otics in the fetus, Pharmacol. Ther., 10, 261– 281, 1980.
   PubMed Web of Science ®Google Scholar
• Itoh, S., Satoh, M., Abe, Y., Hashimoto, H., Yanagimoto, T., and Kamataki, T., A novel form of mouse cytochrome P450 3A (Cyp3a-16). Its cDNA cloning and expression in fetal liver, Eur. J. Biochem., 226, 877–882, 1994.
   PubMedGoogle Scholar
• Nebert, D. W. and Gelboin, H. V., The in vivo and in vitro induction of aryl hydrocarbon hydroxylase in mammalian cells of different species, tissues, strains, and developmental and hormonal status, Arch. Biochem. Biophys., 134, 76–89, 1969.
   PubMed Web of Science ®Google Scholar
• Hulla, J. E. and Juchau, M. R., Developmental aspects of P450IIIA: prenatal activity and inducibility, Drug Metab. Rev., 20, 765– 779, 1989.
   PubMed Web of Science ®Google Scholar
• Miller, M. S., Transplacental lung carcino-genesis: a pharmacogenetic mouse model for the modulatory role of cytochrome P450 1A1 on lung cancer initiation, Chem. Res. Toxicol., 7, 471–481, 1994.
   PubMed Web of Science ®Google Scholar
• Yaffe, S. J., Rane, A., Sjöqvist, F., Boréus, L.-O., and Orrenius, S., The presence of a monooxygenase system in human fetal liver microsomes, Life Sci., 9, 1189–1200, 1970.
   Web of Science ®Google Scholar
• Krauer, B. and Dayer, P., Fetal drug metabolism and its possible clinical inplications, Clin. Pharmacokinet. 21. 70–80, 1991.
   PubMed Web of Science ®Google Scholar
• Leroux, J. P., Cresteil, T., and Marie, S., Ontogeny and regulation of drug metabolism in humans, Dev. Pharmacol. Ther., 13, 63–69, 1989.
   PubMedGoogle Scholar
• Pasanen, M., Pelkonen, O., Kauppila, A., Park, S. S., Friedman, F. K., and Gelboin, H. V., Characterization of human fetal hepatic cytochrome P-450-associated 7-ethoxyreso-rufin O-deethylase and aryl hydrocarbon hy-droxylase activities by monoclonal antibodies, Dev. Pharmacol. Ther., 10, 125–132, 1987.
   PubMedGoogle Scholar
• Yang, H.-Y.L., Namkung, M. J., and Juchau, M. R., Expression of functional cy-tochrome P4501A1 in human embryonic hepatic tissues during organogenesis, Biochem. Pharmacol., 49, 717–726, 1995.
   PubMed Web of Science ®Google Scholar
• Murray, G. I., Foster, C. O., Barnes, T. S., Weaver, R. J., Snyder, C. P., Ewen, S. W. B., Melvin, W. T., and Burke, M. D., Cyto-chrome P450IA expression in adult and fetal human liver, Carcinogenesis, 13, 165–169, 1992.
   PubMed Web of Science ®Google Scholar
• Shimada, T., Yamazaki, H., Mimura, M., Wakamiya, N., Ueng, Y.-F., Guengerich, F. P., and Inui, Y., Characterization of mi-crosomal cytochrome P450 enzymes involved in the oxidation of xenobiotic chemicals in human fetal livers and adult lungs, Drug Metab. Dispos., 24, 515–522, 1996.
   PubMed Web of Science ®Google Scholar
• Omiecinski, C. J., Redlich, C. A., and Costa, P., Induction and developmental expression of cytochrome P450IA1 messenger RNA in rat and human tissues, Cancer Res., 50, 4315– 4321, 1990.
   PubMed Web of Science ®Google Scholar
• Mäenpää, J., Rane, A., Raunio, H., Honkakoski, P., and Pelkonen, O., Cyto-chrome P450 isoforms in human fetal tissues related to phenobarbital-inducible forms in the mouse, Biochem. Pharmacol., 45, 899–907, 1993.
   PubMed Web of Science ®Google Scholar
• Cazeneuve, C., Pons, G., Rey, E., Treluyer, J.-M., Cresteil, T., Thiroux, G., D’athis, P., and Olive, G., Biotransformation of caffeine in human liver microsomes from foetuses, neo-nates, infants and adults, Br. J. Clin. Pharmacol., 37, 405–412, 1994.
   PubMed Web of Science ®Google Scholar
• Ratanasavanh, D., Beaune, P., Morel, F., Flinois, J.-P., Guengerich, F. P., and Guillouzo, A., Intralobular distribution and quantitation of cytochrome P-450 enzymes in human liver as a function of age, Hepatology, 13, 1142–1151, 1991.
   PubMed Web of Science ®Google Scholar
• Cresteil, T., Beaune, P., Kremers, P., Celier, C., Guengerich, F. P., and Leroux, J. P.,Immunoquantification of epoxide hydroxylase and cytochrome P-450 isozymes in fetal and adult human liver microsomes, Eur. J. Bio-chem., 151, 345–350, 1985.
   Google Scholar
• Pons, C., Dansette, P. M., Amar, C., Jaouen, M., Wolf, C. R., Gregeois, J., Homberg, J. C., and Mansuy, D., Detection of human hepatitis anti-liver kidney microsomes (LKM2) auto-antibodies on rat liver sections is predominantly due to reactivity with rat liver P-450 IIC11, J. Pharmacol. Exp. Ther., 259, 1328–1334, 1991.
   PubMed Web of Science ®Google Scholar
• Umberhauer, D. R., Martin, M. V., Lloyd, R. S., and Guengerich, F. P., Cloning and sequence determination of a complementary DNA related to human liver microsomal cyto-chrome P-450 S-mephenytoin 4-hydroxylase, Biochemistry, 26, 1094–1099, 1987.
   PubMed Web of Science ®Google Scholar
• Shimada, T., Misono, K. S., and Guengerich, F. P., Human liver microsomal cytochrome P-450 mephenytoin 4-hydroxylase, a prototype of genetic polymorphism in oxidative drug metabolism, J. Biol. Chem., 261, 909–921, 1986.
   PubMed Web of Science ®Google Scholar
• Ladona, M. G., Lindström, B., Thyr, C., Dun-Ren, P., and Rane, A., Differential foetal development of the O- and N-demethylation of codeine and dextromethorphan in man, Br. J. Clin. Pharmacol., 32, 295–302, 1991.
   PubMed Web of Science ®Google Scholar
• Treluyer, J.-M., Jacqz-Aigrain, E., Alvarez, F., and Cresteil, T., Expression of CYP2D6 in developing human liver, Eur. J. Biochem., 202, 583–588, 1991.
   PubMedGoogle Scholar
• Jacqz-Aigrain, E. and Cresteil, T., Cyto-chrome P450-dependent metabolism of dextro-methorphan: fetal and adult studies, Dev. Pharmacol. Ther., 18, 161–168, 1992.
   PubMedGoogle Scholar
• Komori, M., Nishio, K., Fujitani, T., Ohi, H., Kitada, M., Mima, S., Itahashi, K., and Kamataki, T., Isolation of a new human fetal liver cytochrome P450 cDNA clone: evidence for expression of a limited number of forms of cytochrome P450 in human fetal livers, Arch. Biochem. Biophys., 272, 219–225, 1989.
   PubMed Web of Science ®Google Scholar
• Jones, S. M., Boobis, A. R., Moore, G. E., and Stanier, P. M., Expression of CYP2E1 during human fetal development: methylation of the CYP2E1 gene in human fetal and adult liver samples, Biochem. Pharmacol., 43, 1876– 1879, 1992.
   PubMed Web of Science ®Google Scholar
• Wrighton, S. A., Molowa, D. T., and Guzelian, P. S., Identification of a cytochrome P-450 in human fetal liver related to glucocor-ticoid-inducible cytochrome P-450HLp in the adult, Biochem. Pharmacol., 37, 3053–3055, 1988.
   PubMed Web of Science ®Google Scholar
• Vieira, I., Sonnier, M., and Cresteil, T., Developmental expression of CYP2E1 in the human liver. Hypermethylation control of gene expression during the neonatal period, Eur. J. Biochem., 238, 476–483, 1996.
   PubMedGoogle Scholar
• Wu, D. and Cederbaum, A. I., Expression of cytochrome P4502E1 in rat fetal hepatocyte culture, Mol. Pharmacol., 49, 802–807, 1996.
   PubMed Web of Science ®Google Scholar
• Carpenter, S. J., Lasker, J. M., and Raucy,J. L., Expression, induction, and catalytic activity of the ethanol-inducible cytochrome P450 (CYP2E1) in human fetal liver and hepatocytes, Mol. Pharmacol., 49, 260–268, 1996.
   PubMed Web of Science ®Google Scholar
• Yang, H.-Y.L., Lee, Q. P., Rettie, A. E., and Juchau, M. R., Functional cytochrome P4503A isoforms in human embryonic tissues: expression during organogenesis, Mol. Pharmacol., 46, 922–928, 1994.
   PubMed Web of Science ®Google Scholar
• Wrighton, S. A. and VandenBranden, M., Isolation and characterization of human fetal liver cytochrome P450HLp2: a third member of the P450III gene family, Arch. Biochem. Bio-phys., 268, 144–151, 1989.
   PubMed Web of Science ®Google Scholar
• Komori, M., Nishio, K., Ohi, H., Kitada, M., and Kamataki, T., Molecular cloning and sequence analysis of cDNA containing the entire coding region for human fetal liver cyto-chrome P-450, J. Biochem., 105, 161–163, 1989.
   PubMed Web of Science ®Google Scholar
• Lacroix, D., Sonnier, M., Moncion, A., Cheron, G., and Cresteil, T., Expression of CYP3A in the human liver. Evidence that the shift between CYP3A7 and CYP3A4 occurs immediately after birth, Eur. J. Biochem., 247, 625–634, 1997.
   PubMedGoogle Scholar
• Mäenpää, J., Pelkonen, O., Cresteil, T., and Rane, A., The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver, J. Steroid. Biochem. Molec. Biol., 44, 61–67, 1993.
   PubMed Web of Science ®Google Scholar
• Cresteil, T., Beaune, P., Kremers, P., Flinois, J.-P., and Leroux, J.-P., Drug-metabolizing enzymes in human foetal liver: partial resolution of multiple cytochromes P 450, Pediatr. Pharmacol., 2, 199–207, 1982.
   PubMedGoogle Scholar
• Kitada, M., Kamataki, T., Itahashi, K., Rikihisa, T., and Kanakubo, Y., P-450 HFLa, a form of cytochrome P-450 purified from human fetal livers, is the 16a-hydroxy-lase of dehydroepiandrosterone 3-sulfate, J. Biol. Chem., 262, 13534–13537, 1987.
   PubMed Web of Science ®Google Scholar
• Rane, A., Henningson, S., Ask, B., and Ladona, M. G., Comparison of human fetal hepatic and adrenal cytochrome P450 activities with some major gestational steroids and ethylmorphine as substrates, J. Steroid. Bio-chem. Molec., Biol. 43, 335–341, 1992.
   PubMed Web of Science ®Google Scholar
• Ryan, K. J., Placental synthesis of steroid hormones, in Maternal-Fetal Endocrinology, Tulchinsky, D. and Ryan, K. J., Eds., W. B. Saunders Company, Philadelphia, 1980, 3.
   Google Scholar
• Kitamura, R., Sato, K., Sawada, M., Itoh, S., Kitada, M., Komori, M., and Kamataki, T., Stable expression of cytochrome P450IIIA7 cDNA in human breast cancar cell line MCF-7 and its application to cytotoxicity testing, Arch. Biochem. Biophys., 292, 136–140, 1992.
   PubMed Web of Science ®Google Scholar
• Sakuma, T., Kitamura, R., Yokoi, T., and Kamataki, T., Efficient complementary DNA directed expression of human fetal liver cyto-chrome P450 (CYP3A7) in insect cells using baculovirus, Arch. Biochem. Biophys., 11520, 22828–4654, 1995.
   Google Scholar
• Li, Y., Yokoi, T., Kitamura, R., Sasaki, M., Gunji, M., Katsuki, M., and Kamataki, T.,Establishment of transgenic mice carrying human fetus-specific CYP3A7, Arch. Biochem. Biophys., 329, 235–240, 1996.
   PubMed Web of Science ®Google Scholar
• Kitada, M., Taneda, M., Itahashi, K., and Kamataki, T., Four forms of cytochrome P-450 in human fetal livers: purification and their capacity to activate promutagens, Jpn. J. Cancer Res., 82, 426–432, 1991.
   PubMedGoogle Scholar
• Kitada, M., Kato, T., Ohmori, S., Kamataki, T., Itahashi, K., Guengerich, F. P., Rikihisa, T., and Kanakubo, Y., Immunochemical characterization and toxicological significance of P-450HFLb purified from human fetal livers, Biochim. Biophys. Acta, 1117, 301–305, 1992.
   PubMed Web of Science ®Google Scholar
• Kamataki, T., Kitada, M., Komori, M., Yokoi, T., and Kitamura, R., Human fetal liver cytochrome P-450: capacity to form geno-toxic metabolites, Tohoku. J. Exp. Med., 168, 89–95, 1992.
   PubMed Web of Science ®Google Scholar
• Pasanen, M., Rannala, Z., Tooming, A., Sotaniemi, E.A., Pelkonen, O., and Rautio, A., Hepatitis A impairs the function of human hepatic CYP2A6 in vivo, Toxicology, 1997.
   Google Scholar
• Rifkind, A. B., Tseng, L., Hirsch, M., and Lauersen, N. H., Aryl hydrocarbon hydroxy-lase activity and microsomal cytochrome content of human fetal tissues, Cancer Res., 38, 1572–1577, 1978.
   PubMed Web of Science ®Google Scholar
• Pelkonen, O., Arvela, P., and Kärki, N. T., 3,4-Benzpyrene and N-demetylaniline metabolizing enzymes in the immature human foetus and placenta, Acta Pharmacol. Toxicol., 30, 385–395, 1971.
   PubMedGoogle Scholar
• Pelkonen, O., Differential inhibition of aryl hydrocarbon hydroxylase in human foetal liver, adrenal gland and placenta, Acta Pharmacol. Toxicol., 41, 306–316, 1977.
   PubMedGoogle Scholar
• Lee, Q. P., Fantel, A. G., and Juchau, M. R., Human embryonic cytochrome P450s: phenox-azone ethers as probes for expression of functional isoforms during organogenesis, Biochem. Pharmacol., 42, 2377–2385, 1991.
   PubMed Web of Science ®Google Scholar
• Namkung, M. J., Yang, H.-Y. L., and Juchau, M. R., Cytochrome P-450-dependent biotransformation of 2-acetylaminofluorene in cell-free preparations of human embryonic hepatic, adrenal, renal, pulmonary, and cardiac tissues, Drug Metab., Dispos., 22, 331–337, 1994.
   PubMed Web of Science ®Google Scholar
• Kato, T., Nakasa, H., Ohmori, S., Kamataki, T., Itahashi, K., Shimada, T., Rikihisa, T., and Kitada, M., Possible occurence of P450 related to P450 HFLb in extrahepatic tissues of human fetuses and its contribution to metabolic activation of promutagens, Mutat. Res., 310, 73–77, 1994.
   PubMed Web of Science ®Google Scholar
• Kitada, M., Kamataki, T., Itahashi, K., Rikihisa, T., Kato, R., and Kanakubo, Y.,Immunochemical examination of cytochrome P-450 in various tissues of human fetuses using antibodies to human fetal cytochrome P-450, P-450 HFLa, Biochem. Biophys. Res. Commun., 131, 1154–1159, 1985.
   PubMed Web of Science ®Google Scholar
• Ladona, M. G., Park, S.-S., Gelboin, H. V., Hammar, L., and Rane, A., Monoclonal antibody directed detection of cytochrome P-450 (PCN) in human fetal liver, Biochem. Pharmacol., 37, 4735–4741, 1988.
   PubMed Web of Science ®Google Scholar
• Gilham, D. E., Cairns, W., Paine, M. J. I., Modi, S., Poulsom, R., Roberts, G. C. K., and Wolf, C. R., Metabolism of MTPT by cytochrome P4502D6 and the demonstration of 2D6 mRNA in human foetal and adult brain by in situ hybridization, Xenobiotica, 27, 111– 125, 1997.
   PubMed Web of Science ®Google Scholar
• Boutelet-Bochan, H., Huang, Y., and Juchau, M. R., Expression of CYP2E1 during embryogenesis and fetogenesis in human cephalic tissues: Implications for the fetal alcohol syndrome, Biochem. Biophys. Res. Commun., 238, 443–447, 1997.
   PubMed Web of Science ®Google Scholar
• Stoilov, I., Akarsu, A. N., and Sarfarazi, M., Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21, Hum. Mol. Genet., 6, 641–647, 1997.
   PubMed Web of Science ®Google Scholar
• Jounaidi, Y., Guzelian, P. S., Maurel, P., and Vilarem, M.-J., Sequence of the 5¢-flank-ing region of CYP3A5: comparative analysis with CYP3A4 and CYP3A7, Biochem. Bio-phys. Res. Commun., 205, 1741–1747, 1994.
   PubMed Web of Science ®Google Scholar
• Schuetz, E. G., Schuetz, J. D., Strom, S. C., Thompson, M. T., Fisher, R. A., Molowa, D. T., Li, D., and Guzelian, P. S., Regulation of human liver cytochromes P-450 in family 3A in primary and continuous culture of human hepatocytes, Hepatology, 18, 1254– 1262, 1993.
   PubMed Web of Science ®Google Scholar
• Itoh, S., Yanagimoto, T., Tagawa, S., Hashimoto, H., Kitamura, R., Nakajima, Y., Okochi, T., Fujimoto, S., Uchino, J., and Kamataki, T., Genomic organization of human fetal specific P-450IIIA7 (cytochrome P-450HFLa)-related gene(s) and interaction of transcriptional regulatory factor with its DNA element in the 5¢ flanking region, Biochem. Biophys. Acta, 1130, 133–138, 1992.
   PubMed Web of Science ®Google Scholar
• Wiebkin, P., Dees, J. H., Mathis, J. M., and Prough, R. A., Drug metabolism by isolated fetal human hepatocytes in suspension and primary culture, Drug Metab. Dispos., 13, 163– 168, 1985.
   PubMed Web of Science ®Google Scholar
• Lindros, K. O., Zonation of cytochrome P450 expression, drug metabolism and toxicity in liver, Gen. Pharmacol., 28, 191–196, 1997.
   PubMedGoogle Scholar
• Murray, G. I., Barnes, T. S., Sewell, H. F., Ewen, S. W. B., Melvin, W. T., Shaw, P. M., Fowler, J., and Burke, M. D., Cytochrome P-450 localization in normal human adult and foetal liver by immunocytochemistry using a monoclonal antobody against human cyto-chrome P-450, Histochem. J., 19, 537–545, 1987.
   PubMedGoogle Scholar
• Pelkonen, O., Detoxification and toxification processes in the human feto-placental unit, in Drugs and Pregnancy, Maternal Drug Handling—Fetal Drug Exposure, Krauer, B., Krauer, F., Hytten, F. E., and del Pozo, E., Eds., Academic Press, London, 1984, 63.
   Google Scholar
• Iannaccone, P. M., Bossert, N. L., and Connelly, C. S., Disruption of embryonic and fetal development due to preimplantation chemical insults: a critical review, Am. J. Obstet. Gynecol., 157, 476–484, 1978.
   Google Scholar
• Coceani, F., Control of the ductus arterio-sus—a new function for cytochrome P450, en-dothelin and nitric oxide, Biochem. Pharmacol., 48, 1315–1318, 1994.
   PubMed Web of Science ®Google Scholar
• Coceani, F., Kesley, L., Ackerley, C., Rabinovitch, M., and Gelboin, H. V., Cyto-chrome P450 during ontogenic development: occurrence in the ductus arteriosus and other tissues, Can. J. Physiol. Pharmacol., 72, 217– 226, 1994.
   PubMed Web of Science ®Google Scholar
• Pasanen, M. and Pelkonen, O., Human pla-cental xenobiotic and steroid biotransformations catalyzed by cytochrome P450, epoxide hydrolase, and glutathione S-transferase activities and their relationships to maternal cigarette smoking, Drug Metab. Rev., 21, 427–461, 1989.
   PubMed Web of Science ®Google Scholar
• Pasanen, M. and Pelkonen, O., Xenobiotic and steroid-metabolizing monooxygenases catalysed by cytochrome P450 and glutathione S-transferase conjugations in the human placenta and their relationships to maternal cigarette smoking, Placenta, 11, 75–85, 1990.
   PubMed Web of Science ®Google Scholar
• Welch, R. M., Harrison, Y. E., Conney, A. H., Poppers, P. J., and Finster, M., Cigarette smoking: stimulatory effect on metabolism of 3,4-benzopyrene by enzymes in human placenta, Science, 160, 541–542, 1968.
   PubMed Web of Science ®Google Scholar
• Welch, R. M., Harrison, Y. E., Gommi, B. W., Poppers, P. J., Finster, M., and Conney, A. H., Stimulatory effect of cigarette smoking on the hydroxylation of 3,4,-benz-pyrene and the N-demethylase of 3-methyl-4-monomethylaminoazobenzene by enzymes in human placenta, Clin. Pharmacol. Ther., 10, 100–109, 1969.
   PubMed Web of Science ®Google Scholar
• Nebert, D. W., Winker, J., and Gelboin, H. V., Aryl hydrocarbon hydroxylase activity in human placenta from cigarette smoking and nonsmoking women, Cancer Res., 29, 1763– 1769, 1969.
   PubMed Web of Science ®Google Scholar
• Wong, T. K., Everson, R. B., and Hsu, S.-T., Potent induction of human placental mo-nooxygenase activity by previous dietary exposure to polyclorinated biphenyls and their thermal degradation products, Lancet, I, 721–724, 1985.
   Google Scholar
• Juchau, M. R., Human placental hydroxyla-tion of 3,4,-benzpyrene during early gestation and at term, Toxicol. Appl. Pharmacol., 18, 665– 675, 1971.
   PubMed Web of Science ®Google Scholar
• Sanyal, M. K., Li, Y.-L., Biggers, W. J., Satish, J., and Barnea, E. R., Augmentation of polynuclear aromatic hydrocarbon metabolism of human placental tissues of first-trimester pregnancy by cigarette smoke exposure, Am. J. Obstet. Gynecol., 168, 1587–1597, 1993.
   PubMed Web of Science ®Google Scholar
• Pasanen, M., Vahakangas, K., Sotaniemi, E. A., and Pelkonen, O., The effect of cigarette smoking on drug metabolism in the liver and placenta: the use of cotinine in verifying smoking status, Eur. J. Drug Metab. Pharma-cokin., 13, 41–45, 1988.
   PubMed Web of Science ®Google Scholar
• Manchester, D. K., Range of environmentally responsive monooxygenase activities in human placental microsomes determined by direct fluorescence techniques, Biochem. Pharmacol. 30, 757–762, 1981.
   PubMed Web of Science ®Google Scholar
• Jacobson, M., Levin, W., Poppers, P., Wood, A. W., and Conney, A. H., Comparison of the O-dealkylation of 7-ethoxycouma-rin and the hydroxylation of benzo(a)pyrene in human placenta, Clin. Pharmacol. Ther., 16, 701–710, 1974.
   PubMed Web of Science ®Google Scholar
• Pelkonen, O. and Moilanen, M.-L., The specificity and multiplicity of human placental xe-nobiotic-metabolizing monooxygenase system studied by potential substrates, inhibitors and gel electrophoresis, Med. Biol., 57, 306–312, 1979.
   PubMedGoogle Scholar
• Toma, Y., Higashiyama, T., Yarborough, C., and Osawa, Y., Diverse functions of aro-matase: O-deethylation of 7-ethoxycoumarin, Endocrinology, 137, 3791–3796, 1996.
   PubMed Web of Science ®Google Scholar
• Hakkola, J., Mäenpää, J., Mayer, R. T., Park, S. S., Gelboin, H. V., and Pelkonen, O., 7-alkoxyquinoline O-dealkylation by mi-crosomes from human liver and placenta, Br. J. Clin. Pharmacol., 34, 415–420, 1992.
   PubMed Web of Science ®Google Scholar
• Berry, D. L., Zachariah, P. K., Slaga, T. J., and Juchau, M. R., Analysis of the biotransformation of benzo[a]pyrene in human fetal and placental tissues with high-pressure liquid chromatography, Eur. J. Cancer, 13, 667–675, 1977.
   PubMed Web of Science ®Google Scholar
• Rettie, A. E., Heimark, L., Mayer, R. T., Burke, M. D., Trager, W. F., and Juchau, M. R., Stereo and regioselective hydroxyla-tion of warfarin and selective O-dealkylation of phenoxazone ethers in human placenta, Bio-chem. Biophys. Res. Commun., 126, 1013–1021, 1985.
   PubMed Web of Science ®Google Scholar
• Song, B.-J., Gelboin, H. V., and Park, S. S., Monoclonal antibody-directed radioimmuno-assay detects cytochrome P-450 in human placenta and lymphocytes, Science, 228, 490–492, 1985.
   PubMed Web of Science ®Google Scholar
• Fujino, T., Park, S. S., West, D., and Gelboin, H. V., Phenotyping of cytochrome P-450 in human tissues with monoclonal antibodies, Proc. Natl. Acad. Sci. USA, 79, 3682– 3686, 1982.
   PubMed Web of Science ®Google Scholar
• Pelkonen, O., Pasanen, M., Kuha, H., Gachalyi, B., Kairaluoma, M., Sotaniemi, E. A., Park, S. S., Friedman, F. K., and Gelboin, H. V., The effect of cigarette smoking on 7-ethoxyresorufin O-deethylase and other monooxygenase activities in human liver: analysis with monoclonal antobodies, Br. J. Clin. Pharmacol., 22, 125–134, 1986.
   PubMed Web of Science ®Google Scholar
• Pasanen, M., Haaparanta, T., Sundin, M., Sivonen, P., Vähäkangas, K., Raunio, H., Hines, R., Gustafsson, J.-Å., and Pelkonen, O., Immunochemical and molecular biological studies on human placental cigarette smoke-in-ducible cytochrome P-450-dependent mono-oxy-genase activities, Toxicology, 62, 175–187, 1990.
   PubMed Web of Science ®Google Scholar
• Manchester, D. K. and Jacoby, E. H., Sensitivity of human placental monooxygenase activities to maternal smoking, Clin. Pharmacol. Ther. 30, 687–692, 1981.
   PubMed Web of Science ®Google Scholar
• Pasanen, M., Taskinen, T., Sotaniemi, E. A., Kairaluoma, M., and Pelkonen, O., Inhibitor panel studies of human hepatic and placental cytochrome P-450-associated mono-oxygenase activities, Pharmacol. Toxicol., 62, 311–317, 1988.
   PubMedGoogle Scholar
• Wong, T. K., Domin, B. A., Bent, P. E., Blanton, T. E., Anderson, M. W., and Philpot, R. M., Correlation of placental microsomal activities with protein detected by antibodies to rabbit cytochrome P-450 isozyme 6 in preparations from humans exposured to polychlori-nated biphenyls, quaterphenyls, and dibenzo-furans, Cancer Res., 46, 999–1004, 1986.
   PubMed Web of Science ®Google Scholar
• Pasanen, M., Stenbäck, F., Park, S. S., Gelboin, H. V., and Pelkonen, O., Immuno-histochemical detection of human placental cy-tochrome P-450-associated mono-oxygenase system inducible by maternal cigarette smoking, Placenta, 9, 267–275, 1988.
   PubMed Web of Science ®Google Scholar
• Pasanen, M., Raunio, H., and Pelkonen, O., Freezing affects the activity and subcellular distribution profile of human placental xenobiotic- and steroid-metabolizing enzymes, Placenta, 6, 527–535, 1985.
   PubMed Web of Science ®Google Scholar
• Zhang, L., Connor, E.E., Chegini, N., and Shiverick, K. T., Modulation by benzo[a]py-rene of epidermal growth factor receptors, cell proliferation, and secretion of human chorionic gonadotropin in human placental cell lines, Biochem. Pharmacol., 50, 1171–1180, 1995.
   PubMed Web of Science ®Google Scholar
• Sesardic, D., Pasanen, M., Pelkonen, O., and Boobis, A. R., Differential expression and regulation of the members of the cytochrome P450IA gene subfamily in human tissues, Carcinogene-sis, 11, 1183–1188, 1990.
   PubMed Web of Science ®Google Scholar
• Hakkola, J., Pasanen, M., Hukkanen, J., Pelkonen, O., Mäenpää, J., Edwards, R. J., Boobis, A. R., and Raunio, H., Expression of xenobiotic-metabolizing cytochrome P450 forms in human full-term placenta, Biochem. Pharmacol., 51, 403–411, 1996.
   PubMed Web of Science ®Google Scholar
• Botto, F., Seree, E., Khyari, S. E., de Sousa, G., Massacrier, A., Placidi, M., Cau, P., Pellet, W., Rahmani, R., and Barra, Y.,Tissue-specific expression and methylation of the human CYP2E1 gene, Biochem. Pharmacol., 48, 1095–1103, 1994.
   PubMed Web of Science ®Google Scholar
• Hakkola, J., Raunio, H., Purkunen, R., Pelkonen, O., Saarikoski, S., Cresteil, T., and Pasanen, M., Detection of cytochrome P450 gene expression in human placenta in first trimester of pregnancy, Biochem. Pharmacol., 52, 379–383, 1996.
   PubMed Web of Science ®Google Scholar
• Rasheed, A., Hines, R. N., and McCarver-May, D. G., Variation in induction of human placental CYP2E1: Possible role is susceptibility to fetal alcohol syndrome, Toxicol. Appl. Pharmacol., 144, 396–400, 1997.
   PubMed Web of Science ®Google Scholar
• Schuetz, J. D., Kauma, S., and Guzelian, P. S., Identification of the fetal liver cyto-chrome CYP3A7 in human endometrium and placenta, J. Clin. Invest., 92, 1018–1024, 1993.
   PubMed Web of Science ®Google Scholar
• Edwards, R. J., Singleton, A. M., Murray,B. P., Davies, D. S., and Boobis, A. R., Shortsynthetic peptides exploited for reliable and specific targeting of antibodies to the C-termini ofcytochrome P450 enzymes, Biochem. Pharmacol., 49, 39–47, 1995.
   PubMed Web of Science ®Google Scholar
• Murray, G. I., Barnes, T. S., Sewell, H. F., Ewen, S. W. B., Melvin, W. T., and Burke, M. D., The immunocytochemical localisation and distribution of cytochrome P-450 in normal human hepatic and extrahepatic tissues with a monoclonal antibody to human cytochrome P-450, Br. J. Clin. Pharmacol., 25, 465–475, 1988.
   PubMed Web of Science ®Google Scholar
• Pienimäki, P., Lampela, E., Hakkola, J., Arvela, P., Raunio, H., and Vähäkangas, K., Pharmacokinetics of oxcarbazepine and carbamazepine in human placenta, Epilepsia, 38, 309–316, 1997.
   PubMed Web of Science ®Google Scholar
• Simpson, E. R., Mahendroo, M. S., Means, G. D., Kilgore, M. W., Hinshelwood, M. M., Graham-Lorence, S., Amarneh, B., Ito, Y., Fisher, C. R., Michael, M. D., Mendelson,C. R., and Bulun, S. E., Aromatase cyto-chrome P450, the enzyme responsible for estrogen biosynthesis, Endocrine Rev., 15, 342–355, 1994.
   PubMed Web of Science ®Google Scholar
• Pasanen, M., Human placental aromatase activity: use of a C18 reverse-phased cartridge for separation of tritiated water or steroid metabolites in placentas from both smoking and non-smoking mothers in vitro, Biol. Res. Pregn., 6, 94–99, 1985.
   PubMedGoogle Scholar
• Meigs, R. A., The constitutive 7-ethoxycou-marin O-deethylase activity of human placen-tal microsomes: relationship to aromatase, Bio-chem. Biophys. Res. Commun., 145, 1012–1018, 1987.
   PubMed Web of Science ®Google Scholar
• Sawada, M., Kitamura, R., Norose, T., Kitada, M., Itahashi, K., and Kamataki, T.,Metabolic activation of aflatoxin B1 by human placental microsomes, J. Toxicol. Sci., 18, 129– 132, 1993.
   PubMedGoogle Scholar
• Manchester, D. K., Gordon, S. K., Golas, C. L., Roberts, E. A., and Okey, A. B., Ahreceptor in human placenta: stabilization bymolybdate and characterization of binding of2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methylcholanterene and benzo(a)pyrene, Cancer Res., 47, 4861–4868, 1987.
   PubMed Web of Science ®Google Scholar
• Dolwick, K. M., Schmidt, J. V., Carver, L. A., Swanson, H. I., and Bradfield, C. A., Cloning and expression of a human Ah receptor cDNA, Mol. Pharmacol., 44, 911–917, 1993.
   PubMed Web of Science ®Google Scholar
• Landers, J. P. and Bunce, N. J., The Ah receptor and the mechanism of dioxin toxicity, Biochem. J., 276, 273–287, 1991.
   PubMed Web of Science ®Google Scholar
• Sogawa, K., Nakano, R., Kobayashi, A., Kikuchi, Y., Ohe, N., Matsushita, N., and Fujii-Kuriyama, Y., Possible function of Ah receptor nuclear translocator (Arnt) homodi-mer in transcriptional regulation, Proc. Natl. Acad. Sci. USA, 92, 1936–1940, 1995.
   Google Scholar
• Antonsson, C., Arulampalam, V., Whitelaw, M. L., Pettersson, S., and Poellinger, L.,Constitutive function of the basic helix-loop-helix/PAS factor Arnt, J. Biol. Chem., 270, 13968–13972, 1995.
   PubMed Web of Science ®Google Scholar
• Swanson, H. I., Chan, W. K., and Bradfield, C. A., DNA binding specificities and pairing rules of the Ah receptor, ARNT, and SIM proteins, J. Biol. Chem., 270, 26292–26302, 1995.
   PubMed Web of Science ®Google Scholar
• Sutter, T. R., Guzman, K., Dold, K. M., and Greenlee, W. F., Targets for dioxin: genes for plasminogen activator inhibitor-2 and inter-leukin-1b, Science, 254, 415–418, 1991.
   PubMed Web of Science ®Google Scholar
• Christou, M., Savas, Ü., Spink, D. C., Gierthy, J. F., and Jefcoate, C. R., Co-expression of human CYP1A1 and a human analog of cyto-chrome P450-EF in response to 2,3,7,8-tetra-chloro-dibenzo-p-dioxin in human mammary carcinoma-derived MCF-7 cells, Carcinogen-esis, 15, 725–732, 1994.
   PubMed Web of Science ®Google Scholar
• Gradin, K., Wilhelmsson, A., Poellinger, L., and Berghard, A., Nonresponsiveness of normal human fibroblasts to dioxin correlates with the presence of a constitutive xenobiotic response element-binding factor, J. Biol. Chem., 268, 4016–4068, 1993.
   PubMed Web of Science ®Google Scholar
• Pirani, B. B. K., Smoking during pregnancy, Obstet. Gynec. Survey, 33, 1–13, 1978.
   PubMedGoogle Scholar
• Werler, M. M., Pober, B. R., and Holmes, L. B., Smoking and pregnancy, Teratology, 32, 473–481, 1985.
   PubMedGoogle Scholar
• Everson, R. B., Randerath, E., Santella, R. M., Cefalo, R. C., Avitts, T. A., and Randerath, K., Detection of smoking-related covalent DNA adducts in human placenta, Science, 231, 54–57, 1986.
   PubMed Web of Science ®Google Scholar
• Manchester, D. K., Weston, A., Choi, J.-S., Trivers, G. E., Fennessey, P. V., Quintana, E., Farmer, P. B., Mann, D. L., and Harris, C. C., Detection of benzo[a]pyrene diol epox-ide-DNA adducts in human placenta, Proc. Natl. Acad. Sci. USA, 85, 9243–9247, 1988.
   PubMed Web of Science ®Google Scholar
• Manchester, D. K., Wilson, V. L., Hsu, I.-C., Choi, J.-S., Parker, N. B., Mann, D. L., Weston, A., and Harris, C. C., Synchronous fluorescence spectroscopic, immunoaffinity chro-matographic and 32P-postlabeling analysis of human placental DNA known to contain ben-zo[a]pyrene diol epoxide adducts, Carcino-genesis, 11, 553–559, 1990.
   Google Scholar
• Manchester, D., Bowman, E. D., Parker, N. B., Caporaso, N. E., and Weston, A.,Determinants of polycyclic aromatic hydrocar-bon-DNA adducts in human placenta, Cancer Res., 52, 1499–1503, 1992.
   PubMed Web of Science ®Google Scholar
• Vähäkangas, K., Raunio, H., Pasanen, M., Sivonen, P., Park, S.-S., Gelboin, H. V., and Pelkonen, O., Comparison of the formation of benzo[a]pyrene diolepoxide-DNA adducts in vitro by rat and human microsomes: evidence for the involvement of P-450IA1 and P-450IA2, J. Biochem. Toxicol., 4, 79–86, 1989.
   PubMedGoogle Scholar
• Hansen, C., Asmussen, I., and Autrup, H., Detection of carcinogen-DNA adducts in human fetal tissues by the 32-postlabeling procedure, Environ. Health Perspect., 99, 229–231, 1993.
   PubMed Web of Science ®Google Scholar
• Gallagher, J. E., Everson, R. B., Lewtas, J., George, M., and Lucier, G. W., Comparison of DNA adduct levels in human placenta from polychlorinated biphenyl exposed women and smokers in which CYP 1A1 levels are similarly elevated, Teratog. Carcinog. Muta-gen., 183–192, 1994.
   Google Scholar
• Hatch, M. C., Warburton, D., and Santella, R. M., Polycyclic aromatic hydrocarbon-DNA adducts in spontaneously aborted fetal tissue, Carcinogenesis, 11, 1673–1675, 1990.
   PubMed Web of Science ®Google Scholar
• Hansen, C., Sorensen, L. D., Asmussen, I., and Autrup, H., Transplacental exposure to tobacco smoke in human-adduct formation in placenta and umbilical cord blood vessels, Tera-tog. Carcinog. Mutagen., 12, 51–60, 1992.
   PubMedGoogle Scholar
• Pelkonen, O., Kärki, N. T., Koivisto, M., Tuimala, R., and Kauppila, A., Maternal cigarette smoking, placental aryl hydrocarbon hydroxylase and neonatal size, Toxicol. Lett. 3, 331–335, 1979.
   Web of Science ®Google Scholar
• Everson, R. B., Randerath, E., Santella, R., Avitts, T. A., Weinstein, I. B., and Randerath, K., Quantitative associations between DNA damage in human placenta, maternal smoking, and birth weight, J. Natl. Cancer Inst., 80, 567– 576, 1988.
   PubMed Web of Science ®Google Scholar
• Huel, G., Girard, F., Nessmann, C., Godin, J., Blot, P., Breart, G., and Moreau, T.,Placental aryl hydrocarbon hydroxylase activity and placental calcifications, Toxicology, 71, 257–266, 1992.
   PubMed Web of Science ®Google Scholar
• Manchester, D. and Jacoby, E., Decreased placental monooxygenase activities associated with birth defects, Teratology, 30, 31–37, 1984.
   PubMedGoogle Scholar
• Manchester, D. K., Parker, N. B., and Bowman, C. M., Maternal smoking increases xenobiotic metabolism in placenta but not umbilical vein endothelium, Pediatr. Res., 18, 1071–1075, 1984.
   PubMed Web of Science ®Google Scholar
• Fisk, N. M. and Storey, G. N. B., Fetal outcome in obstetric cholestasis, Br. J. Obstet. Gynaecol., 95, 1137–1143, 1988.
   PubMedGoogle Scholar
• Pasanen, M., Helin-Martikainen, H.-L., Pelkonen, O., and Kirkinen, P., Intrahepat-ic cholestasis of pregnancy impairs the activities of human placental xenobiotic and steroid metabolizing enzymes in vitro, Placenta, 18, 37–41, 1997.
   PubMed Web of Science ®Google Scholar
• Ostrea, E. M., Porter, T., Balun, J., Wardell, J. N., and Bottoms, S., Effect of chronic maternal drug addiction on placental drug metabolism, Dev. Pharmacol. Ther., 12, 42–48, 1989.
   PubMedGoogle Scholar
• Pineau, T., Fernandez-Salguero, P., Lee, S. S. T., McPhail, T., Ward, J. M., and Gonzalez, F. J., Neonatal lethality associated with respiratory distress in mice lacking cyto-chrome P450 IA2, Proc. Natl. Acad. Sci. USA, 92, 5134–5138, 1995.
   PubMed Web of Science ®Google Scholar
• Liang, H.-C. L., Li, H., McKinnon, R. A., Duffy, J. J., Potter, S. S., Puga, A., and Nebert, D. W., CYP1a2(-/-) null mutant mice develop normally but show deficient drug metabolism, Proc. Natl. Acad. Sci. USA, 93, 1671– 1676, 1996.
   PubMed Web of Science ®Google Scholar
• Lee, S. S. T., Buters, J. T. M., Pineau, T., Fernandez-Salguero, P., and Gonzalez, F. J.,Role of CYP2E1 in the hepatotoxicity of acetaminophen, J. Biol. Chem., 271, 12063– 12067, 1996.
   PubMed Web of Science ®Google Scholar
• Zaphiropoulos, P. G., Mode, A., Norstedt, G., and Gustaffson, J.-Å., Regulation of sexual differentiation in drug and steroid metabolism, Trends Pharmacol. Sci., 10, 149–153, 1989.
   PubMed Web of Science ®Google Scholar
• Fujita, I., Sindhu, R. K., and Kikkawa, Y., Hepatic cytochrome P450 enzyme imprinting in adult rat by neonatal benzo(a)pyrene administration, Pediatr. Res., 37, 646–651, 1995.
   PubMed Web of Science ®Google Scholar
• Park, B. K., Pirmohamed, M., and Kitteringham, N. R., The role of cytochrome P450 enzymes in hepatic and extrahepatic human drug toxicity, Pharmac. Ther., 68, 385– 424, 1995.
   PubMed Web of Science ®Google Scholar