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Research Article

Biochemical Toxicology of Chemical Teratogenesis

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Pages 1-40 | Published online: 26 Sep 2008

References

  • Anderson M. E., Powrie F., Puri R. N., Meister A. Glutathione monoethyl ester: preparation, uptake by tissues, and conversion to glutathione. Arch. Biochem. Biophys. 1985; 239: 538–548
  • Anderson M. E., Meister A. Glutathione monoesters. Anal. Biochem. 1989; 183: 16–20
  • Arlen R. R., Wells P. G. Effect of the cyclooxygenase inhibitor acetylsalicylic acid on thalidomide teratogenicity in New Zealand white rabbits. FASEB J. 1989; 3: A1025
  • Arlen R. R., Wells P. G. Inhibition of thalidomide teratogenicity by acetylsalicylic acid: evidence for prostaglandin H synthetase-catalysed bioactivation of thalidomide to a teratogenic reactive intermediate in the New Zealand white rabbit. J. Pharmacol. Exp. Ther. 1996, In press
  • Arlen R. R., Wells P. G. Extracellular thiol-disulfide status reflecting chemical tox-icity mediated via oxidative stress: validation with paraquat and t-butylhydroperoxide, and implications for phenytoin and thalidomide teratogenicity. FASEB J. 1990; 4: A608
  • Arlen R. A., Wells P. G. Submitted. Extracellular thiol-disulfide status reflecting chemical toxicity mediated via oxidative stress: validation with paraquat and t-butylhydroperoxide, and implications for phenytoin and thalidomide teratogenicity.
  • Ashby R., Davis L., Dewhurst B. B., Espinal R., Penn R. N., Upshall D. G. Aspects of the teratology of cyclophosphamide (NSC-26271). Cancer Treat. Rep. 1976; 60: 477–482
  • Balling R., Haaf M., Maydl R., Metzler M., Beier H. M. Oxidative and conjugative metabolism of diethylstilbestrol by rabbit pre-implantation embryos. Dev. Biol. 1985; 109: 370–378
  • Benson A. J., Martin C. N., Garner R. C. N-(2-Hydroxyethyl)-N[2-(7-guaninyl) ethyl], the putative major DNA adduct of cyclophosphamide in vitro and in vivo in the rat. Biochem. Pharmacol. 1988; 37: 2979–2985
  • Bochert G., Platzek R., Rahm U., Webb I. Some new aspects in the study of DNA alkylation in embryonic and fetal tissues. Role of Pharmacokinetics in Prenatal and Perinatal Toxicology, D. Neubert, H.-J. Merker, H. Nau, J Langman. Georg Thieme Verlag, Stuttgart 1978; 253–261
  • Boyd J. A., Harvan D. J., Eling T. E. The oxidation of 2-aminofluorene by prostaglandin endoperoxide synthetase. J. Biol. Chem. 1983; 258: 8246–8254
  • Boyd J. A., Eling T. E. Prostaglandin H synthase-catalyzed metabolism and DNA binding of 2-naphthylamine. Cancer Res. 1987; 47: 4007–4014
  • Boyd J. A., Eling T. E. Evidence for a one-electron mechanism of 2-aminofluorene oxidation by prostaglandin H synthase and horseradish peroxidase. J. Biol. Chem. 1984; 259: 13885–13896
  • Braun A. G., Harding F. A., Weinreb S. L. Teratogen metabolism: thalidomide activation is mediated by cytochrome P-450. Toxicol. Appl. Pharmacol. 1986; 82: 175–179
  • Brierly C. H., Burchell B. Human UDP-glucuronosyl transferases: chemical defence, jaundice and gene therapy. Bioessays 1993; 15: 749–754
  • Buehler B. A. Epoxide hydrolase activity and fetal hydantoin syndrome. Proc. Greenwood Genet. Cent. 1984; 3: 109–110
  • Buehler B. A., Delimont D., VanWaes M., Finnell R. H. Prenatal prediction of risk of the fetal hydantoin syndrome. N. Engl. J. Med. 1990; 322: 1567–1572
  • Burchell B. Observations of uridine diphos-phate glucuronyltransferase activity towards oestriol and xenobiotics in developing and cultured tissues from mouse and man. Biochem. Soc. Trans. 1973; 1: 1212–1214
  • Burchell B., Dutton G. J. Delayed induction by phenobarbital of UDP-glucuro-nyltransferase activity towards bilirubin in fetal liver. Biol. Neonate 1975; 26: 122–128
  • Burchell B., Coughtrie M. W. H. UDP-glucuronosyltransferase. Pharmacol. Ther. 1989; 43: 261–289
  • Burchell B., Coughtrie M. W. H., Jansen P. L. M. Function and regulation of UDP-glucuronosyltransferase genes in health and liver disease: report of the seventh international workshop on glucuronidation, September 1993, Pitlochry, Scotland. Hepatology 1994; 20: 1622–1630
  • Byczkowski J. Z., Kulkarni A. P. Lipoxygenase-catalyzed epoxidation of benzo[a]pyrene-7,8-dihydrodiol. Biochem. Biophys. Res. Commun. 1989; 159: 1199–1205
  • Carpenter S. P., Raucy J. L. CYP2E1: a putative role in chemical-mediated teratoge-nesis. Proc. Int. Soc. Study Xenobiot. 1995; 8: 238
  • Chung C. S., Myrianthopoulos N. C. Factors affecting risks of congenital malformations. The National Foundation March of Dimes. Original Articles Series. 1975; Vol. 11.
  • Chung A.-S., Maines M. D., Reynolds W. A. Inhibition of the enzymes of glutathione metabolism by mercuric chloride in the rat kidney: reversal by selenium. Biochem. Pharmacol. 1982; 31: 3093–3100
  • Datta K., Kulkarni A. P. Oxidative metabolism of aflatoxin B1 by lipoxygenase purified from human term placenta and intrau-terine conceptal tissues. Teratology 1994; 50: 311–317
  • Degen G. H., Eling T. E., McLachlan J. A. Oxidative metabolism of diethylstil-bestrol by prostaglandin synthetase. Cancer Res. 1982; 42: 919–923
  • DeSesso J. M. Cell death and free radicals: a mechanism for hydroxyurea teratogenesis. Med. Hypoth. 1979; 5: 937–951
  • DeSesso J. M., Scialli A. R., Goeringer G. C. D-Mannitol, a specific hydroxyl free radical scavenger, reduces the developmental toxicity of hydroxyurea in rabbits. Teratology 1994; 49: 248–259
  • DeSesso J. M., Goeringer G. C. Ethoxyquin and nordihydroguaiaretic acid reduce hydroxyurea developmental toxicity. Reprod. Toxicol. 1990; 4: 267–275
  • Dierickx P. J. In vitro inhibition of the soluble glutathione s-transferases from rat liver by heavy metals. Enzyme 1982; 27: 25–32
  • Dirven H. A., Venekamp A. M.J. C., van Ommen B., Van Bladeren P. J. The interaction of glutathione with 4-hydroxy-cyclophos-phamide and phosphoramide mustard, studied by 32P nuclear magnetic resonance spectros-copy. Chem. Biol. Interact. 1994; 93: 185–196
  • Doecke C. J., Veronese M. E., Pond S. M., Miners J. O., Birkett D. J., Sansom L. N., McManus M. E. Relationship between phenytoin and tolbutamide hydroxylations in human liver microsomes. Br. J. Clin. Pharmacol. 1991; 1: 125–130
  • Dutton G. J. Glucuronide-forming enzymes. Handbook of Experimental Pharmacology Brodie and Gillette. Springer-Verlag., Berlin 1971; Vol. 28: 378–400, 2
  • Edmonds L., Hatch M., Holmes L., Kline J., Letz G., Levin B., Miller R., Shrout P., Stein Z., Warburton D., Weinstock M., Whorton R. D., Wyrobek A. Report of panel II: guidelines for reproductive studies in exposed human populations. Guidelines for Studies of Human Populations Exposed to Mutagenic and Reproductive Hazards, A. D. Bloom. March of Dimes Birth Defects Foundation, White Plains, NY 1981
  • Eriksson U. J., Borg L. A. H. Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro. Diabetologia 1991; 34: 325–331
  • Eriksson U. J., Borg L. A. H. Diabetes and embryonic malformations: role of sub-strate-induced free-oxygen radical production for dysmorphogenesis in cultured rat embryos. Diabetes 1993; 42: 411–419
  • Fantel A. G., Greenaway J. C., Juchau M. R., Shepard T. H. Teratogenic bioactivation of cyclophosphamide in vitro. Life Sci. 1979; 25: 67–72
  • Fantel A. G. Culture of whole rodent embryos in teratogen screening. Teratogen. Carcinogen. Mutagen. 1982; 2: 231–234
  • Fantel A. G., Pereson R. E., Tracy J. W., Juchau M. R. Niridazole metabolism by rat embryos in vitro. Teratology 1988; 37: 213–221
  • Fantel A. G., Barber C. V., Carda M. B., Tumbic R. W., Mackler B. Studies of the role of ischemia/reperfusion and superoxide anion radical production in the teratogenicity of cocaine. Teratology 1992; 46: 293–300
  • Faustman-Watts E. M., Greenaway J. C., Namkung M. J., Fantel A. G., Juchau M. R. Teratogenicity in vitro of 2-acetylaminofluorene: role of biotransforma-tion. Teratology 1983; 27: 19–28
  • Faustman-Watts E. M., Giachelli C. M., Juchau M. R. Carbon monoxide inhibits monooxygenation by the conceptus and embryotoxic effects of proteratogens in vitro. Toxicol. Appl. Pharmacol. 1986; 83: 590–595
  • Filler R., Lew K. J. Developmental onset of mixed-function oxidase activity in preimplantation mouse embryos. Proc. Natl. Acad. Sci. U.S.A. 1981; 78: 6991–6995
  • Finnell R. H., Chernoff C. F. Gene-teratogen interactions: an approach to understanding the metabolic basis of birth defects. Pharmacokinetics in Teratogenesis, H. Nau, W. Scott. CRC Press., New York 1987; Vol. 2.: 97–109
  • Finnell R. H., Kerr B. M., van Waes M., Steward R. L., Levy R. H. Protection from phenytoin-induced congenital malformations by coadministration of the antiepileptic drug stiripentol in a mouse model. Epilepsia 1994; 35: 141–148
  • Fort D. J., Stover E. L., Rayburn J. R., Huli M., Bantle J. A. Evaluation of the developmental toxicity of trichloroeth-ylene and detoxification metabolites using Xenopus. Teratogen. Carcinogen. Mutagen. 1993; 13: 35–45
  • Frank A. A., Collier J. M., Forsyth C. S., Zeng W., Stoner G. D. Ellagic acid embryoprotection in vitro: distribution and effects on DNA adduct formation. Teratology 1993; 47: 275–280
  • Frischer H., Bowman J. E., Carson P. E., Rieckmann K. H., Willerson D., Colwell E. J. Erythrocyte glutathione reductase, glucose-6-phosphate dehydrogenase and 6-phosphogluconic dehydrogenase deficiencies in populations of the United States, South Vietnam, Iran and Ethiopia. J. Lab. Clin. Med. 1973; 81: 603
  • Gibson J. E., Becker B. A. Effect of phenobarbital and SKF 525-A on the teratogenicity of cyclophosphamide in mice. Teratology 1968; 1: 393–398
  • Gonzalez F. J. Genetic polymorphism and cancer susceptibility. Fourteenth Sapporo Cancer Seminar. Cancer Res. 1995; 55: 710–715
  • Gordon G. B., Spielberg S. P., Blake D. A., Balasubramanian V. Thalidomide teratogenesis: evidence for a toxic arene oxide metabolite. Proc. Natl. Acad. Sci. U.S.A. 1981; 78: 2545–2548
  • Gordon G. B., Spielberg S. P., Blake D. A., Balasubramanian V. Thalidomide teratogenesis: evidence for a toxic arene oxide metabolite. Proc. Natl. Acad. Sci. U.S.A. 1983; 78: 2545–2548
  • Goto Y., Noda Y., Mori T., Nakano M. Increased generation of reactive oxygen species in embryos cultured in vitro. Free Rad. Biol. Med. 1993; 15: 69–75
  • Greenaway J. C., Fantel A. G. Enhancement of rifampin teratogenicity in cultured rat embryos. Toxicol. Appl. Pharmacol. 1983; 69: 81–88
  • Guengerich F. P., Shimada T. Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem. Res. Toxicol. 1991; 4: 391–407
  • Hales B. F. Modification of the mutagenic-ity and teratogenicity of cyclophosphamide in rats with inducers of the cytochromes P-450. Teratology 1981a; 24: 1–11
  • Hales B. F. Modification of the teratogenicity and mutagenicity of cyclophosphamide with thiol compounds. Teratology 1981b; 23: 373–381
  • Halliwell B., Gutteridge J. M. C. Protection against oxidants in biological systems: the superoxide theory of oxygen toxicity. Free Radicals in Biology and Medicine, B. Halliwell, J. M. C. Gutteridge. Oxford University Press, London 1989; 86–187
  • Halliwell B., Kaur H., Ingelman-Sundberg M. Hydroxylation of salicylate as an assay for hydroxyl radicals: a cautionary note. Free Rod. Biol. Med. 1991; 10: 439–441
  • Hansen D. K. The embryotoxicity of phenytoin: an update on possible mechanisms. Proc. Soc. Exp. Biol Med. 1991; 197: 361–368
  • Harbison R. D. Chemical-biological reactions common to teratogenesis and mutagen-esis. Environ. Health Perspect. 1978; 24: 87–100
  • Harbison R. D., Becker B. A. Effects of phenobarbital or SKF525A pretreatment on diphenylhydantoin disposition in pregnant mice. Toxicol. Appl. Pharmacol. 1971; 20: 573–581
  • Harbison R. D., Becker B. A. Comparative embryotoxicity of diphenylhydantoin and some of its metabolites in mice. Teratology 1974; 10: 237–242
  • Harris C., Stark K. L., Juchau M. R. Glutathione status and the incidence of neural tube defects elicited by direct acting terato-gens in vitro. Teratology 1988; 37: 577–590
  • Harris C., Stark K. L., Luchtel D. L., Juchau M. R. Abnormal neurulation induced by 7-hydroxy-2-acetylaminofluorene and acetaminophen: evidence for catechol metabolites as proximate dysmorphogens. Toxicol. Appl. Pharmacol. 1989; 101: 432–447
  • Heinonen O. P., Slone D., Shapiro S. Birth Defects and Drugs in Pregnancy. PSG., Littleton, MA 1977; 450: 127
  • High K. A., Kubow S. n-3 fatty acids inhibit defects and fatty acid changes caused by phenytoin in early gestation in mice. Lipids 1994; 29: 771–778
  • Hiranruengchok R., Harris C. Glutathione oxidation and embryotoxicity elicited by diamide in the developing rat conceptus in vitro. Toxicol. Appl. Pharmacol. 1993; 120: 62–71
  • Hsieh L.-L., Hsieh T.-T. Detection of aflatoxin B1DNA adducts in human placenta and cord blood. Cancer Res. 1993; 53: 1278–1280
  • Hume R. Proc. 7th Annual Workshop on Glucuronidation and the UDP-Glucurono-syltransferases, Pitlochry, Scotland, 1993, 7
  • Iyer P., Martin J. E., Irvin T. R. Role of biotransformation in the in vitro preimplan-tation embryotoxicity of naphthalene. Toxicology 1991; 66: 257–270
  • Jellum E., Marstein S., Skullerud K., Munthe E. Glutathione in pyroglutamic aciduria (5-oxoprolinuria) and rheumatoid arthritis. Functions of Glutathione: Biochemical, Physiological, Toxicological and Clinical Aspects, A. Larsson, S. Orrenius, A. Holmgren, B. Mannervik. Raven Press, New York 1983; 325–336
  • Jones A. L., Hume R., Bamford K. J., Coughtrie W. H. Estrogen and phenol sulfotransferase activities in human fetal lung. Early Hum. Dev. 1992; 28: 65–77
  • Juchau M. R. Enzymatic bioactivation and inactivation of chemical teratogens and trans-placental carcinogens/mutagens. The Biochemical Basis of Chemical Teratogenesis. Elsevier, New York 1981; 63–94
  • Juchau M. R., Bark D. H., Shewey L. M., Greenaway J. C. Generation of reactive dysmorphogenic intermediates by rat embryos in culture: effects of cytochrome P-450 inducers. Toxicol. Appl. Pharmacol. 1985a; 81: 533–544
  • Juchau M. R., Giachelli C. M., Fantel A. G., Greenaway J. C., Shepard T. H., Faustman-Watts E. M. Effects of 3-me-thylcholanthrene and phenobarbital on the capacity of embryos to bioactivate teratogens during organogenesis. Toxicol. Appl. Pharmacol. 1985b; 80: 137–147
  • Juchau M. R., Fantel A. G., Harris C., Beyer B. K. The potential role of redox cycling as a mechanism for chemical teratogenesis. Environ. Health Perspect. 1986; 70: 131–136
  • Juchau M. R., Lee Q. P., Fantel A. G. Xenobiotics biotransformation/bioactivation in organogenesis-stage conceptal tissues: implications for embryotoxicity and teratogenesis. Drug Metab. Rev. 1992; 24: 195–238
  • Jurima-Romet M., Shek P. N. Lung uptake of liposome-entrapped glutathione after intratracheal administration. J. Pharm. Pharmacol. 1991; 43: 6–10
  • Kanekal S., Kehrer J. P. Metabolism of cyclophosphamide by lipoxygenases. Drug Metab. Dispos. 1993; 22: 74–78
  • Kappus H. Overview of enzyme systems involved in bio-reduction of drugs and in redox cycling. Biochem. Pharmacol. 1986; 35: 1–6
  • Keller R. J., Hinson J. A. Mechanism of acetaminophen-stimulated NADPH oxidation catalyzed by the peroxidase-H2O2 system. Drug Metab. Dispos. 1991; 19: 184–187
  • Kim P. M., Wells P. G. Salicylate hy-droxylation as an in vivo probe for hydroxyl radical formation in CD-1 mice: relevance to phenytoin teratogenicity. Toxicologist 1993; 13: 253
  • Kim P. M., Wells P. G. Phenytoin hydroxyl radical formation: characterization by enhanced salicylate hydroxylation. Mol. Pharmacol. 1996; 49: 172–181
  • Kim P. K., Winn L. M., Parman T., Wells P. G. Submitted. UDP-glucuronosyltrans-ferase-mediated protection against in vitro DNA oxidation, micronucleus formation and embryotoxicity initiated by phenytoin and its major metabolite 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH)
  • Kitada M., Kamataki T. Cytochrome P450 in human fetal liver: significance and fetal-specific expression. Drug Metab. Rev. 1994; 26: 2305–2323
  • Kitchin K. T., Schmid B. P., Sanyal M. K. Teratogenicity of cyclophosphamide in a coupled microsomal activating/embryo culture system. Biochem. Pharmacol. 1981; 30: 59–64
  • Kromidas L., Trombetta L. D., Jamall I. S. The protective effects of glutathione against methyl mercury cytotoxicity. Toxicol. Lett. 1990; 51: 67–80
  • Kubow S. Inhibition of isotretinoin teratogenicity by acetylsalicylic acid pretreatment in mice. Teratology 1992; 45: 55–63
  • Kubow S., Wells P. G. In vitro evidence for prostaglandin synthetase-catalyzed bio-activation of phenytoin to a free radical intermediate. Pharmacologist 1986; 28: 195
  • Kubow S., Wells P. G. In vitro evidence for lipoxygenase-catalyzed bioactivation of phenytoin. Pharmacologist 1988; 30: A74
  • Kubow S., Wells P. G. In vitro bioactivation of phenytoin to a reactive free radical intermediate by prostaglandin syn-thetase, horseradish peroxidase and thyroid peroxidase. Mol. Pharmacol. 1989; 35: 504–511
  • Laposa R. R., Wells P. G. Preliminary evaluation of phenytoin teratogenicity in transgenic mice deficient in the p53 tumor suppressor gene. Toxicologist 1995; 15: 161
  • Laposa R. L., Chan K. C., Wilewy M. J., Wells P. G. Enhanced phenytoin embryopathy in p53-deficient mice: characterisation of embryonic p53 genotype and the p53, p21 and Bax DNA damage response proteins. Toxicologist 1996; 16: 997
  • Larsson A., Hagenfeldt L. Hereditary glutathione synthetase deficiency in man. Functions of Glutathione: Biochemical, Physiological, Toxicological, and Clinical Aspects, A. Larsson, S. Orrenius, A. Holmgren, B. Hannervik. Raven Press, New York 1983; 317–324
  • Lear L., Nation R. L., Stupans I. Effects of cyclophosphamide and adriamycin on rat hepatic microsomal glucuronidation and lipid peroxidation. Biochem. Pharmacol. 1992; 44: 747–753
  • Lenz W. Kindliche Missbildungen nach Medikament-Einnahme wahrend der Gravid-itat. Dtsch. Med. Wochenschr. 1961; 86: 2555–2556
  • Lenz W. Thalidomide and congenital anomalies. Lancet 1962; 1: 45
  • Little S. A., Mirkes P. E. DNA cross-linking and single-strand breaks induced by teratogenic concentrations of 4-hydro-peroxycyclophosphamide and phosphoramide mustard in postimplantation rat embryos. Cancer Res. 1987; 47: 5421–5426
  • Liu L., Wells P. G. In vitro and in vivo cytochromes P450- and peroxidase-catalysed formation of phenytoin-DNA adducts in mu-rine maternal hepatic and embryonic tissues. Proc. 10th International Symposium on Microsomes and Drug Oxidations. Toronto, Canada July, 1994a; 555
  • Liu L., Wells P. G. In vivo phenytoin-initiated oxidative damage to proteins and lip-ids in murine maternal hepatic and embryonic tissue organelles: potential molecular targets mediating chemical teratogenesis. Toxicol. Appl. Pharmacol. 1994b; 125: 247–255
  • Liu L., Wells P. G. Potential molecular targets mediating chemical teratogenesis: in vitro peroxidase-catalysed phenytoin metabolism and oxidative damage to proteins and lipids in murine maternal hepatic microsomes and embryonic 9000 g supernatant. Toxicol. Appl. Pharmacol. 1995a; 134: 71–80
  • Liu L., Wells P. G. DNA oxidation as a potential molecular mechanism mediating drug-induced birth defects: phenytoin and structurally related teratogens initiate the formation of 8-hydroxy-2'-deoxyguanosine in vitro and in vivo in murine maternal hepatic and embryonic tissues. Free Rad. Biol. Med. 1995b; 19: 639–648
  • Loch-Caruso R., Baxter C. S. DNA damage and repair in embryonic mouse limbs exposed to teratogenic doses of methyl-nitrosourea. Mutat. Res. 1984; 131: 147–155
  • Loiseau P., Duche B. Potential antiepileptic drugs: stiripentol. Antiepileptic Drugs3rd, R. Levy, R. Mattson, B. Meldrum, J. K. Penry, F. E. Dreifuss. Raven Press, New York 1989; 955–969
  • Lu L.-J. W., Anderson L. M., Jones A. B., Moskal T. J., Salazar J. J., Hokanson J. A., Rice J. M. Persistence, gestation stage-dependent formation and interrelationship of benzo[a]pyrene-induced DNA adducts in mothers' placentae and fetuses of erythroceubs patas monkeys. Carcinogenesis 1993; 14: 1805–1813
  • Lum J. T., Wells P. G. Pharmacological studies on the potentiation of phenytoin ter-atogenicity by acetaminophen. Teratology 1986; 33: 53–72
  • Manson J. Teratogens. Toxicology, The Basic Science of Poisons, C. D. Klaassen, M. D. Amdur, J. Doull. Macmillan, New York 1986; 195–220
  • Marnett L. J., Wlodawer P., Samuelsson B. Co-oxygenation of organic substrates by prostaglandin synthetase of sheep vesicular gland. J. Biol. Chem. 1975; 250: 8510–8517
  • Marnett L. J., Reed G. A., Johnson J. T. Prostaglandin synthase-dependent benzo[a]pyrene oxidation: products of the oxidation and inhibition of their formation by antioxidants. Biochem. Biophys. Res. Commun. 1977; 79: 569–576
  • Marnett L. J., Reed G. A., Dennison D. J. Prostaglandin synthase dependent activation of 7,8-dihydro-7,8-dihydroxylbenzo[a] pyrene to mutagenic derivatives. Biochem. Biophys. Res. Commun. 1978; 82: 210–216
  • Marnett L. J. Prostaglandin synthase mediated metabolism of carcinogens and a potential role for peroxyl radicals as reactive intermediates. Environ. Health Perspect. 1990; 88: 5–12
  • Martz F., Failinger C., Blake D. A. Phenytoin teratogenicity: correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational mouse. J. Pharmacol. Exp. Ther. 1977; 203: 231–239
  • McBride. Thalidomide and congenital abnormalities. Lancet 1961; 2: 1358
  • Mehta A. B. Glucose-6-phosphate dehydro-genase deficiency. Postgrad. Med. J. 1994; 70: 871–877
  • Meister A. Metabolism and transport of glutathione and other gamma-glutamyl compounds. Functions of Glutathione: Biochemical, Physiological, Toxicological, and Clinical Aspects, A. Larsson, S. Orrenius, A. Holmgren, B. Mannervik. Raven Press, New York 1983; 1–93
  • Miranda A. F., Wiley M. J., Wells P. G. Evidence for embryonic peroxidase-catalysed bioactivation and glutathione-depen-dent cytoprotection in phenytoin teratogenic-ity: modulation by eicosatetraynoic acid and buthionine sulfoximine in murine embryo culture. Toxicol. Appl. Pharmacol. 1994; 124: 230–241
  • Mirkes P. E., Little S. A., Beland F. A., Huitfeldt H. S., Poirier M. C. Quantitation and immunohistochemical localization of DNA adducts in rat embryos and associated yolk sac membranes exposed in vitro to N -acetoxy-2-acetylaminofluorene (N-Ac-AAF). Teratogen. Carcinogen. Mutagen. 1991; 11: 93–102
  • Modrich P. Mismatch repair, genetic stability and tumour avoidance. Philos. Trans. R. Soc. London Ser. B. 1995; 347: 89–95
  • Nau H. Retinoidteratogenesis: toxicokinetics and structure-specificity. Arch. Toxicol. 1994; 16(Suppl)118–127
  • Nebert D. W. Genetic differences in drug metabolism: proposed relationship to human birth defects. Handbook of Experimental Pharmacology Teratogenesis and Reproductive Toxicology, E. M. Johnson, D. M. Kochhar. Springer-Verlag, New York 1983; 65: 49–62
  • New D. A. T. Whole embryo culture and the study of mammalian embryos during organo-genesis. Biol. Rev. 1978; 53: 81–122
  • Nicol C. J., Harrison M. L., Laposa R. R., Gimelshtein I. L., Wells P. G. A teratologic suppressor role for p53 in benzo[a]pyrene-treated transgenic p53-defi-cient mice. Nature Genet. 1995; 10: 181–187
  • Nicol C. J., Wells P. G. Glucose-6-phosphate dehydrogenase (G6PD): an embryo-protective role in endogenous oxidative stress and phenytoin teratogenesis. Toxicologist 1996; 16: 1008
  • Nishikido N., Furuyashiki K., Naganuma A., Suzuki T., Imura N. Maternal selenium deficiency enhances the fetolethal tox-icity of methyl mercury. Toxicol. Appl. Pharmacol. 1987; 88: 322–328
  • Nonogaki T., Noda Y., Narimoto K., Umaoka Y., Mori T. Effects of superoxide dismutase on mouse in vitro fertilization and embryo culture system. J. Assist. Reprod. Genet. 1992; 9: 274–280
  • Noda Y., Matsumoto H., Mori T. Superoxide dismutase overcomes 2-cell block in mouse embryos. Acta. Obstet. Gynaecol. Jpn. 1989; 41: 751–752
  • Noda Y., Matsumoto H., Umaoka Y., Tatsumi K., Kishi J., Mori T. Involvement of superoxide radicals in the mouse 2-cell block. Mol. Reprod. Dev. 1991; 28: 356–360
  • Otto S., Marcus C., Pidgeon C., Jefcoate C. A novel adrenocorticotrophin-inducible cytochrome P450 from rat adrenal microsomes catalyzes polycyclic aromatic hydrocarbon metabolism. Endocrinology 1991; 129: 970–982
  • Otto S., Bhattacharyya K. K., Jefcoate C. R. Polycyclic aromatic hydrocarbon metabolism in rat adrenal, ovary and testis microsomes is catalyzed by the same novel cytochrome P450 (P450RAP). Endocrinology 1992; 131: 3067–3076
  • Ornaghi F., Ferrini S., Pratt M., Giavini E. The protective effects of N-acetyl-L-cys-teine against methyl mercury embryotoxicity in mice. Fundam. Appl. Toxicol. 1993; 20: 437–445
  • Ozolins T. R. S., Oglesby L. A., Wiley M. J., Wells P. G. In vitro murine embryopathy of cyclophosphamide in embryos co-cultured with maternal hepatocytes: development and application of a murine embryo-hepatocyte co-culture model. Toxicology 1995a; 102: 259–274
  • Ozolins T. R. S., Wiley M. J., Wells P. G. Phenytoin covalent binding and embryopathy in murine embryos co-cultured with maternal hepatocytes from mouse, rat and rabbit. Biochem. Pharmacol. 1995b; 50: 1831–1840
  • Ozolins T. R. S., Siksay D. L. A., Wells P. G. Selenium-dependent modulation of glutathione peroxidase activities and phenytoin teratogenicity. J. Pharmacol. Exp. Ther. 1996, In press.
  • Panich V. G6PD variants in southern Asian populations. Glucose-6-phosphate Dehy-drogenase, A. Yoshida, E. Beutler. Academic Press, New York 1986; 195–241
  • Pantarotto C., Arbix M., Sezzano P., Abbruzzi R. Studies on 5,5-diphenyl hydantoin irreversible binding to rat liver mi-crosomal proteins. Biochem. Pharmacol. 1982; 31: 1501–1507
  • Parman T., Chen G., Bray T. M., Wells P. G. Bioactivation of phenytoin, thali-domide and related teratogens to a free radical intermediate using prostaglandin H synthase (PHS) or hepatic microsomes: characterization by electron spin resonance (ESR) spec-trometry. Toxicologist 1996; 16: 1260
  • Pillans P. I., Ponzi S. F., Parker M. I. Cyclophosphamide induced DNA strand breaks in mouse embryo cephalic tissue in vivo. Carcinogenesis 1989; 10: 83–85
  • Platzek T., Bochert G., Meister R., Neubert D. Embryotoxicity induced by alkylat-ing agents. VII. Low dose prenatal-toxic risk estimation based on NOAEL risk factor approach, dose-response. Relationships and DNA adducts using methylnitrosourea as a model compound. Teratogen. Carcinogen. Mutagen. 1993; 13: 101–125
  • Platzek T., Bochert G., Rahm T. Embryotoxicity induced by alkylating agents. VIII. DNA adduct formation induced by ethylmethanesulfonate in mouse embryos. Teratogen. Carcinogen. Mutagen. 1994a; 14: 65–73
  • Platzek T., Schwabe R., Rahm U., Bochert G. DNA modification induced by 6-mercaptopurine riboside in murine embryos. Chem. Biol. Interact. 1994b; 93: 59–71
  • Platzek T., Bochert G., Pauli B., Meister R., Neubert D. Embryotoxicity induced by alkylating agents: 5 dose-response relationships of teratogenic effects of methylnitrosourea in mice. Arch. Toxicol. 1988; 62: 411–423
  • Ponz, De Leon M. Cancer-prone hereditary diseases associated with abnormalities of DNA repair. Recent Res. Cancer 1994; 136: 322–331
  • Pottenger L. H., Christou M., Jefcoate C. R. Purification and immunological characterization of a novel cytochrome P450 from C3H/10T1/2 Cells. Arch. Biochem. Biophys. 1991; 286: 488–497
  • Potter D. W., Hinson J. A. Mechanisms of acetaminophen oxidation to N-acetyl-p-benzoquinone imine by horseradish peroxi-dase and cytochrome P450. J. Biol. Chem. 1987; 262: 966–973
  • Radman M., Matic I., Halliday J. A., Taddei F. Editing DNA replication and recombination by mismatch repair: from bacterial genetics to mechanisms of predisposition to cancer in humans. Philos. Trans. R. Soc. London Ser. 1995; B347: 97–103
  • Raucy J. L., Carpenter S. J. The expression of xenobiotic-metabolizing cytochromes P450 in fetal tissues. J. Pharmacol. Toxicol. Methods 1993; 29: 121–128
  • Roberts C. J., Lowe C. R. Where have all the conceptions gone. Where have all the conceptions gone 1975; 1: 498–499
  • Rolfe B. E. Detection of fetal wastage. Fertil. Steril. 1982; 37: 655–660
  • Roy D., Snodgrass W. R. Covalent binding of phenytoin and modulation of diphenylhydantoin metabolism by thiols in A/J mouse liver microsomes. J. Pharmacol. Exp. Ther. 1990; 252: 895–900
  • Roy S. K., Kulkarni A. P. Lipoxygenase: a new pathway for 2-aminofluorene bioactivation. Cancer Lett. 1991; 60: 33–39
  • Saillenfait A.-M., Payan J.-P., Langonne I., Beydon D., Grandclaude M.-C., Sabate J.-P., De Ceaurriz J. Modulation of acry-lonitrile-induced embryotoxicity in vitro by glutathione depletion. Arch. Toxicol. 1993; 67: 164–172
  • Samokyszyn V. M., Sloane B. F., Honn K. V., Mamett L. J. Cooxidation of 13-cis-retinoic acid by prostaglandin H synthase. Biochem. Biophys. Res. Commun. 1984; 124: 430–436
  • Sancar A. Mechanisms of DNA excision repair. Science 1994; 266: 1954–1956
  • Sanyal M. K., Kitchin K. T., Dixon R. L. Anomalous development of rat embryos cultured in vitro with cyclophosphamide and microsomes. Pharmacologist 1979; 21: 231
  • Sanyal S., Wells P. G. Reduction in phenytoin teratogenicity by pretreatment with the antioxidant d-a-tocopherol acetate (vitamin E) in CD-1 mice. Toxicologist 1993; 13: 252
  • Sato J. Glutathione S-transferases and hepatocarcinogenesis. Jpn. J. Cancer Res. 1988; 79: 556–572
  • Savas U., Bhattacharyya K. K., Christou M., Alexander D. L., Jefcoate C. R. Mouse cytochrome P-450EF, representative of a new 1B subfamily of cytochrome P-450s. J. Biol Chem. 1994; 269: 14905–14911
  • Shanks M. J., Wiley M. J., Kubow S., Wells P. G. Phenytoin teratogenicity: role of enzymatic bioactivation in a murine embryo culture model. Teratology 1989; 40: 311–320
  • Shum S., Jensen N. M., Nebert D. W. The murine Ah locus: in utero toxicity and teratogenesis associated with genetic differences in benzo[a]pyrene metabolism. Teratology 1979; 20: 365–376
  • Slott V. L., Hales B. F. Enhancement of the embryotoxicity of acrolein, but not phosphoramide mustard by glutathione depletion in rat embryos in vitro. Biochem. Pharmacol. 1987; 36: 2019–2025
  • Smith R. G., Daves G. D., Jr, Lynn R. K., Gerber N. Hydantoin ring glucuroni-dation: characterization of a new metabolite of 5,5-diphenyl hydantoin in man and the rat. Biomed. Mass Spectrom. 1977; 4: 275–279
  • Spielberg S. P. Acetaminophen toxicity in lymphocytes heterozygous for glutathione syn-thetase deficiency. Can. J. Physiol. Pharmacol. 1985; 63: 468–471
  • Stark K. L., Harris C., Juchau M. R. Embryotoxicity elicited by inhibition of gamma-glutamyltransferase by acivicin and transferase antibodies in cultured rat embryos. Toxicol. Appl. Pharmacol. 1987; 89: 88–97
  • Strickler S. M., Dansky L. V., Miller M. A., Seni M. H., Andermann E., Spielberg S. P. Genetic predisposition to phenytoin induced birth defects. Lancet 1985; 2: 746–749
  • Suntres Z. E., Shek P. N. Incorporation of a-tocopherol in liposomes promotes the retention of liposome-encapsulated glutathione in the rat lung. J. Pharm. Pharmacol. 1994; 46: 23–28
  • Terlouw G. D. C., Namkung M. J., Juchau M. R., Bechter R. F. In vitro embryotoxicity of N -methyl-N-(7-propoxynaphtha-lene-2-ethyl)-hydroxylamine (QAB): evidence for Af-dehydroxylated metabolite as a proximate dysmorphogen. Teratology 1993; 48: 431–439
  • Tonoki H. Establishment of Chinese hamster ovary cell lines with reduced expression of glutathione reductase after antisense-ori-ented gene transfection and assessment of the sensitivity to oxidant injury. Hokkaido J. Med. Sci. 1994; 69: 1261–1274
  • Uetrecht J., Zahid N. N-chlorination of phenytoin by myeloperoxidase to a reactive metabolite. Chem. Res. Toxicol. 1988; 1: 148–151
  • Veronese M. E., Mackenzie P. I., Doecke C. J., McManus M. E., Miners J. O., Birkett D. J. Tolbutamide and phenytoin hy-droxylations by cDNA-expressed human liver cytochrome P4502C9. Biochem. Biophys. Res. Commun. 1991; 3: 1112–1118
  • Vienneau D. S., DeBoni U., Wells P. G. Potential genoprotective role for UDP-glucuronosyltransferases (UGTs) in chemical carcinogenesis: initiation of micronuclei by benzo[a]pyrene and benzo[e]pyrene in UGT-deficient cultured rat skin fibroblasts. Cancer Res. 1995; 55: 1045–1051
  • Wang M. Y., Lu L. J. W. Differential effect of gestation stage on benzo[a]pyrene-induced micronucleus formation and/or cova-lent DNA modifications in mice. Cancer Res. 1990; 50: 2146–2151
  • Wells P. G., Gesicki I. B. Modulation of phenytoin teratogenicity by exogenous and endogenous inhibitors of oxidative drug metabolism. Proceedings of the 9th International Congress of Pharmacology. London, U.K 1984; 1772
  • Wells P. G. Chemical teratogenesis. Principles of Medical Pharmacology, 5th, H. Kalant, W. H. E. Roschlau. B. C. Decker, Toronto 1989; 644–657
  • Wells P. G., Vo H. P. N. Effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on phenytoin embryopathy. Toxicol. Appl. Pharmacol. 1989; 97: 398–405
  • Wells P. G., Harbison R. D. Significance of the phenytoin reactive arene oxide intermediate, its oxepin tautomer, and clinical factors modifying their role in phenytoin-in-duced teratology. Phenytoin-Induced Teratology and Gingival Pathology, T. M. Hassell, M. C. Johnston, K. H. Dudley. Raven Press, New York 1980; 83–108
  • Wells P. G., Obilo F. C., De Morais S. M. F. Benzo[a]pyrene embryopathy in rats genetically deficient in bilirubin UDP-glucuronyl transferase. FASEB J. 1989a; 3: A1025
  • Wells P. G., Nagai M. K., Spano Greco G. Inhibition of trimethadione and dimethadione teratogenicity by the cyclo-oxygenase inhibitor acerylsalicylic acid: a unifying hypothesis for the teratologic effects of hydantoin anticonvulsants and structurally related compounds. Toxicol. Appl. Pharmacol. 1989b; 97: 406–414
  • Wells P. G., Zubovits J. T., Wong S. T., Molinari L. M., Ali S. c. Modulation of phenytoin teratogenicity and embryonic cova-lent binding by acetylsalicylic acid, caffeic acid and alpha-phenyl-N-t-butylnitrone: implications for bioactivation by prostaglandin synthetase. Toxicol. Appl. Pharmacol. 1989; 97: 192–202
  • Wells P. G., Davidovich O., Mark T. M. Inhibition of murine phenytoin teratogenicity by the iron chelator deferoxamine. Toxicologist 1991; 11: 293
  • Wells P. G., Srivastava S. Enhancement of phenytoin fetal and maternal toxicity by low-level exposure to methylmercury. Toxicologist 1992; 12: 309
  • Wells P. G., Williams L. M. Effect of phenytoin on embryonic soluble thiols and disulfides in murine embryo culture. Toxicologist 1994; 14: 164
  • Wells P. G., Leeder J. S., Winn L. M. Phenytoin-initiated protein oxidation in murine embryo culture: a potential molecular mechanism mediating phenytoin teratogenicity. Toxicologist 1995; 15: 276
  • Wells P. G., Kim P. M. UDP-glucuronosyltransferase (UGT)-mediated genoprotection in phenytoin- and 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH)-initiated DNA oxidation and micronucleus formation. Toxicologist 1996; 16: 1201
  • Wells P. G., Kim P. M., Nicol C. J., Parman T., Winn L. M. Reactive intermediates. Handbook of Experimental Pharmacology: Drug Toxicity in Embryonic Development chap. 17, R. J. Kavlock, G. P. Daston. Springer-Verlag, in press, Heidelberg 1996
  • Williams G. M., Weisburger J. H. Chemical carcinogenesis. Casarett and Doull's Toxicology: The Basic Science of Poisons, 4th, M. O. Amdur, J. Doull, C. D. Klaassen. McGraw-Hill, New York 1991; 127–200
  • Wilson J. G. Present status of drugs as teratogens in man. Teratology 1973; 7: 3–16
  • Winn L. M., Wells P. G. Benzo[a] pyrene-initiated DNA and protein oxidation in murine embryo culture: a potential molecular mechanism mediating benzo[a]pyrene teratogenicity. Proc. 27th Annual Symposium of the Society of Toxicology of Canada. 1994; 77
  • Winn L. M., Wells P. G. Free radical-mediated mechanisms of anticonvulsant teratogenicity. Eur. J. Neurol. 1995a; 2((Suppl. 4))5–29
  • Winn L. M., Wells P. G. Phenytoin-initiated DNA oxidation in murine embryo culture, and embryoprotection by the anti-oxidative enzymes superoxide dismutase and catalase: evidence for reactive oxygen species mediated DNA oxidation in the molecular mechanism of phenytoin teratogenicity. Mol. Pharmacol. 1995b; 48: 112–120
  • Winn L. M., Wells P. G. Enhancement of embryonic activity of superoxide dismutase (SOD) and inhibition of benzo[a]pyrene embryopathy in embryo culture by exogenous addition of SOD. Toxicologist 1996; 16: 1249
  • Winn L. M., Wells P. G. Evidence for embryonic prostaglandin H synthase-catalyzed bioactivation and reactive oxygen species-mediated oxidation of macromolecules in phenytoin and benzo[a]pyrene teratogenesis. Free Rad. Biol. Med. 1996, In press
  • Wong M., Wells P. G. Effects of N -acetylcysteine on fetal development and phenytoin teratogenicity in mice. Teratogen. Carcinogen. Mutagen. 1988; 8: 65–79
  • Wong M., Wells P. G. Modulation of embryonic glutathione reductase and phenytoin teratogenicity by l,3-bis(2-chloroethyl)-l-nitrosourea. J. Pharmacol. Exp. Ther. 1989; 250: 336–342
  • Wong M., Helston L. M. J., Wells P. G. Enhancement of murine phenytoin teratogenicity by the gamma-glutamylcysteine synthetase inhibitor buthionine sulfoximine and the glutathione depletor diethylmaleate. Teratology 1989; 40: 127–141
  • Wrighton S. A., Stevens J. C. The human hepatic cytochromes P450 involved in drug metabolism. Crit. Rev. Toxicol. 1992; 22: 1–21
  • Wubah J. A., Ibrahim M. M., Gao X., Nguyen D., Pisano M. M., Knudsen T. B. Ter-atogen-induced eye defects mediated by p53-dependent apoptosis. Curr. Biol. 1996; 6: 60–69
  • Yang H.-Y. L., Lee Q. P., Rettie A. E., Juchau M. R. Functional cytochrome P4503A isoforms in human embryonic tissues: expression during organogenesis. Mol. Pharmacol. 1994; 46: 922–928
  • Yoneyama M., Ogata A., Hiraga K. Irreversible in vivo binding of thiabendazole to macromolecules in pregnant mice and its relation to teratogenicity. Fd. Chem. Toxic. 1985; 23: 733–736
  • Yoneyama M., lchikawa H. Irreversible in vivo and in vitro binding of thiabendazole to tissue protein of pregnant mice. Fd. Chem. Toxic. 1986; 24: 1283–1286
  • Yu W. K., Wells P. G. Evidence for lipoxygenase-catalyzed bioactivation of phenytoin to a teratogenic reactive intermediate: in vitro studies using linoleic acid-dependent soybean lipoxygenase, and in vivo studies using pregnant CD-1 mice. Toxicol. Appl. Pharmacol. 1995; 131: 1–12
  • Ziegler M. H., Grafton T. F., Hansen D. K. The effect of tolbutamide on rat embryonic development in vitro. Teratology 1993; 48: 45–51
  • Zimmerman E. F., Potturi R. B., Resnick E., Fisher J. E. Role of oxygen free radicals in cocaine-induced vascular disruption in mice. Teratology 1994; 49: 192–201

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