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Research Article

Carcinogenicity and Modification of the Carcinogenic Response by bha, Bht, and Other Antioxidants

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Pages 109-150 | Published online: 26 Sep 2008

References

  • Deichmann W. B., Gables C., Clemmer F. J. J., Rakoczy R., Bianchine J. Toxicity of ditertiarybutylmethylphenol. Arch. Ind. Health 1955; 11: 93
  • Hodge H. C., Fassett D. W., Mayard E. A., Downs W. L., Coye R. D. Chronic feeding studies of butylated hydroxyanisole in dogs. Toxicol. Appl. Pharmacol. 1964; 6: 512
  • Hodge H. C., Maynard E. A., Down W. L., Ashton J. K., Selerno L. L. Tests on mice for evaluating carcinogenicity. Toxicol. Appl. Pharmacol. 1966; 9: 583
  • Kerr R., Lefeure A., Lane B. P., Lieber C. S. Liver growth induced by butylated hydroxytoluene (BHT). Clin. Res. 1967; 14: 229
  • Lane B. P., Lieber C. S. Effects of butylated hydroxytoluene on the ultrastructure of rat hepatocytes. Lab. Invest. 1967; 16: 342
  • Kohn R. R. Effect of antioxidants on life-span of C57BL mice. J. Gerontol 1971; 26: 378
  • Marino A. A., Mitchell J. T. Lung damage to mice following intraperitoneal injection of butylated hydroxytoluene. Proc. Soc. Exp. Biol. Med. 1972; 140: 122
  • Grantham P. H., Weisburger J. H., Weisburger E. K. Effect of the antioxidant butylated hydroxytoluene (BHT) on the metabolism of the carcinogens N-2-fluorenylacetamide and N-hydroxy-N-2-fluorenylacetamide. Food Cosmet. Toxicol. 1973; 11: 209
  • Witschi H., Saheb W. Simulation of DNA synthesis in mouse lung following intraperitoneal injection of butylated hydroxytoluene, Proc. Soc. Exp. Biol. Med. 1974; 147: 690
  • Branen A. L. Toxicology and biochemistry of butylated hydroxyanisole and butylated hydroxytoluene. J. Am. Oil Chem. Soc. 1975; 52: 59
  • Saheb W., Witschi H. Lung growth in mice after a single dose of butylated hydroxytoluene. Toxicol. Appl. Pharmacol. 1975; 33: 309
  • Allen J. R. Long-term antioxidant exposure effects on female primates. Arch. Environ. Health 1976; 31: 47
  • Witschi H., Kacew S., Tsang B. K., Williams D. Biochemical parameters of BHT induced cell growth in mouse lung. Chem. Biol. Interact. 1976; 12: 29
  • Adamson I. Y. R., Bowden D. H., Cote M. G., Witschi H. Lung injury induced by butylated hydroxytoluene: cytodynamic and biochemical studies in mice. Lab. Invest. 1977; 36: 26
  • Berry D. L., DiGiovanni J., Juchau M. R., Bracken W. M., Gleason G. L., Salga R. J. Lack of tumor-promoting ability of certain environmental chemicals in a two-stage mouse skin tu-morigenesis assay. Res. Commun. Chem. Path. Pharmacol. 1978; 20: 101
  • Evaluation of the Health Aspects of Butylated Hydroxyanisole as a Food Ingredient. National Technical Information Service. Food and Drug Administration, Springfield, Va 1978
  • Witschi H., Lock A. Toxicity of butylated hydroxytoluene in mouse following oral administration. Toxicology 1978; 9: 137
  • Bioassay of Butylated Hydroxytoluene (BHT) for Possible Carcinogenicity, DHEN Publ. No. (NIH) 79-1706. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. U.S. Government Printing Office, Washington, DC 1979
  • Reddy B. S., Furuya K., Hanson D., DiBello J., Berke B. Effect of dietary butylated hy-droxyanisole on methylazoxymethanol acetate-induced toxicity in mice. Food Chem. Toxicol. 1982; 20: 853
  • Hanig J. P., Yoder P. D., Krop S. Protection with butylated hydroxytoluene and other compounds against intoxication and mortality caused by hexachlorophene. Food Chem. Toxicol. 1984; 22: 185
  • Furukawa K., Maeura Y., Furukawa N. T., Williams G. M. Induction by butylated hydroxytoluene of rat liver γ-glutamyl transpeptidase activity in comparison to expression in carcinogen-induced altered lesions. Chem. Biol. Interact. 1984; 48: 43
  • Dacre J. C., Denz F. A. The metabolism of butylated hydroxyanisole in the rabbit. Biochem. J. 1956; 64: 777
  • Astill B. D., Fassett D. W., Roudabush R. L. The metabolism of phenolic antioxidants. II. The metabolism of butylated hydroxyanisole in the rat. Biochem. J. 1960; 75: 543
  • Dacre J. C. The metabolism of 3,5-di-tert-butyl-4-hydroxytoluene and 3,5-di-tert-butyl-4-hydroxy-benzoic acid in the rabbit. Biochem. J. 1961; 78: 758
  • Astill B. D., Mills J., Fassett D. W., Roudabush R. L., Terhaar C. J. Fate of butylated hydroxyanisole in man and dog. Agric. Food Chem. 1962; 10: 315
  • Golder W. S., Ryan A. J., Wright S. E. The urinary excretion of tritiated butylated hydroxyanisole and butylated hydroxytoluene in the rat. J. Pharm. Pharmacol. 1962; 14: 268
  • Ladomery L. G., Ryan A. J., Wright S. E. The urinary excretion of14C-labelled butylated hydroxytoluene by the rat. J. Pharm. Pharmacol. 1963; 15: 771
  • Daniel J. W., Gage J. C. The absorption and excretion of butylated hydroxytoluene (BHT) in the rat. Food Cosmet. Toxicol. 1965; 3: 405
  • Hathway D. E. Metabolic fate in animals of hindered phenolic antioxidants in relation to their safety evaluation and antioxidant function. Adv. Food Res. 1966; 15: 1
  • Daniel J. W., Gage J. C., Jones D. I., Stevens M. A. Excretion of butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA) by man. Food Cosmet. Toxicol. 1967; 5: 475
  • Ladomery L. G., Ryan A. J., Wright S. E. The excretion of [14C]butylated hydroxytoluene in the rat. J. Pharm. Pharmacol. 1967; 19: 383
  • Ladomery L. G., Ryan A. J., Wright S. E. The biliary metabolites of butylated hydroxytoluene in the rat. J. Pharm. Pharmacol. 1967; 19: 388
  • Daniel J. W., Gage J. C., Jones D. I. The metabolism of 3,5-di-tert-butyl-4-hydroxytoluene in the rat and man. Biochem. J. 1968; 106: 783
  • Holder G. M., Ryan A. J., Watson T. R., Wiebe L. I. The metabolism of butylated hydroxytoluene, (3,5-di-t-butyl-4-hydroxytoluene) in man. J. Pharm. Pharmacol. 1970; 22: 375
  • Holder G. M., Ryan A. J., Watson T. R., Wiebe L. I. The biliary metabolism of butylated hydroxytoluene (3,5-di-t-butyl-4-hydroxytoluene) and its derivatives in the rat. J. Pharm. Pharmacol. 1970; 22: 832
  • Daniel J. W., Gage J. C. The metabolism of BHT by man. Food Cosmet. Toxicol. 1971; 9: 320
  • Shaw Y., Chen C. Ring hydroxylation of di-t-butylhydroxytoluene by rat liver microsomal preparation. Biochem. J. 1972; 128: 1285
  • Daniel J. W., Green T., Phillips P. J. Metabolism of the phenolic antioxidant 3,5-di-tert-butyl-4-hydroxyanisole (topanol 354). I. Excretion and tissue distribution in man, rat and dog. Food Cosmet. Toxicol. 1973; 11: 771
  • Daniel J. W., Green T., Phillips P. J. Metabolism of the phenolic antioxidant 3,5-di-tert-butyl-4-hydroxyanisole (topanol 354). II. Biotransformation in man, rat and dog. Food Cosmet. Toxicol. 1973; 11: 781
  • Daniel J. W., Green T., Phillips P. J. Metabolism of the phenolic antioxidant 3,5-di-tert-butyl-4-hydroxyanisole (topanol 354). III. The metabolism in rats of the major autoxidation product, 2,6-di-tert-butyl-p-benzoquinone. Food Cosmet. Toxicol. 1973; 11: 793
  • Chen C., Shaw Y. Cyclic metabolic pathway of a butylated hydroxytoluene by rat liver microsomal fractions. Biochem. J. 1974; 144: 497
  • Speier J. L., Wattenberg L. W. Alterations in microsomal metabolism of benzolalpyrene in mice fed butylated hydroxyanisole. J. Natl. Cancer Inst. 1975; 55: 469
  • Takahashi O., Hiraga K. 2,6-Di-tert-butyl-4-methylene-2,5-cyclohexadienone: a hepatic metabolite of butylated hydroxytoluene in rats. Food Cosmet. Toxicol. 1979; 17: 451
  • Takahashi O., Hiraga K. Excretion of dietary butylated hydroxytoluene by the rat. Toxicol. Lett. 1980; 6: 287
  • Minegishi K., Watanabe M., Yamaha T. Distribution of butylated hydroxyanisole and its conjugates in the tissues of rats. Chem. Pharm. Bull. 1981; 29: 1377
  • Rahimtula A. D., Jernström B., Dock L., Moldeus P. Effects of dietary and in vitro 2(3)-t-butyl-4-hydroxyanisole and other phenols on hepatic enzyme activities in mice. Br. J. Cancer 1982; 45: 935
  • Young-Nam C., Henry S. H. Comparative effects of dietary administration of 2(3)-tert-butyl-4-hydroxyanisole and 3,5-di-tert-butyl-4-hydroxytoluene on several hepatic enzyme activities in mice and rats. Cancer Res. 1982; 42: 2609
  • Rahimtula A. In vitro metabolism of 3-t-butyl-4-hydroxyanisole and its irreversible binding to proteins. Chem. Biol. Interact. 1983; 45: 125
  • Takahashi O., Hiraga K. The role of 2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone (BHT quinone methide) in the metabolism of butylated hydroxytoluene. Food Chem. Toxicol. 1983; 21: 279
  • Matsuo M., Mihara K., Okuno M., Ohdawa H., Miyamoto J. Comparative metabolism of 3,5-di-tert-butyl-4-hydroxytoluene (BHT) in mice and rats. Food Chem. Toxicol. 1984; 22: 345
  • Wattenberg L. W. Inhibition of carcinogenic and toxic effects of polycyclic hydrocarbons by phenolic antioxidants and ethoxyquin. J. Natl. Cancer Inst. 1972; 48: 1425
  • Wattenberg L. W. Inhibition of chemical carcinogen-induced pulmonary neoplasia by butylated hydroxyanisole. J. Natl. Cancer Inst. 1973; 50: 1541
  • Ulland B. M., Weisburger J. H., Yamamoto R. S., Weisburger E. K. Antioxidants and carcinogenesis: butylated hydroxytoluene, but not diphenyl-p-phenylenediamine, inhibits cancer induction by N-2-fluorenylacetamide and by N-hydroxy-N-fluorenylacetamide in rats. Food Cosmet. Toxicol. 1973; 11: 199
  • Wattenberg L. W. Inhibition of carcinogenic and toxic effects of polycyclic hydrocarbons by several sulfur-containing compounds. J. Natl. Cancer Inst. 1974; 52: 1583
  • Wattenberg L. W. Inhibitors of colon carcinogenesis. Cancer 1977; 40: 2432
  • Slaga T. J., Bracke W. M. The effects of antioxidants on skin tumor initiation and aryl hydrocarbon hydroxylase. Cancer Res. 1977; 37: 1631
  • Weisburger E. K., Evarts R. P., Wenk M. L. Inhibitory effect of butylated hydroxytoluene (BHT) on intestinal carcinogenesis in rats by azoxymethane. Food Cosmet. Toxicol. 1977; 15: 139
  • Wattenberg L. W. Inhibition of chemical carcinogenesis. J. Natl. Cancer Inst. 1978; 60: 11
  • Clapp N. K., Tyndall R. L., Satterfield L. C., Klima W. C., Bowles N. D. Selective sex-related modification of diethylnitrosamine-induced carcinogenesis in BALB/c mice by concomitant administration of butylated hydroxytoluene. J. Natl. Cancer Inst. 1978; 61: 177
  • Clapp N. K., Boweles N. D., Satterfield L. C., Klima W. C. Selective protective effect of butylated hydroxytoluene against 1,2-dimethylhydrazine carcinogenesis in BALB/c mice. J. Natl. Cancer Inst 1979; 63: 1081
  • King M. M., Bailey D. M., Gibson D. D., Pitha J. V., McCay P. B. Incidence and growth of mammary tumors induced by 7,12-dimethylbenz(a) anthracene as related to the dietary content of fat and antioxidant. J. Natl. Cancer Inst. 1979; 63: 657
  • Wattenberg L. W. Inhibitory effects of butylated hydroxyanisole on methylazoxymethanol acetate-induced neoplasia of the large intestine and on nicotinamide adenine dinucleotide-dependent alcohol dehydrogenase activity in mice. J. Natl. Cancer Inst. 1979; 63: 219
  • Wattenberg L. W., Jerina D. M., Lam L. K. T., Yagi H. Neoplastic effects of oral administration oftrans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene and their inhibition by butylated hydroxyanisole. J. Natl. Cancer Inst 1979; 62: 1103
  • Wattenberg L. W. Inhibitors of chemical carcinogens. J. Environ. Pathol. Toxicol. 1980; 3: 35
  • Cohen B. I., Raicht R. F. Plant sterols: protective role in chemical carcinogenesis. Inhibition of Tumor Induction and Development, M. S. Zedeck, M. Lipkin. Plenum Press, New York 1981; 189
  • King M. M., McCay P. B., Kosanke S. D. Comparison of the effect of butylated hydroxytoluene on N-nitroso-methylurea and 7,12-dimethylbenz(a]anthracene-induced mammary tumors. Cancer Lett. 1981; 14: 219
  • Kim H. L., Johnes L. P. Protective effects of butylated hydroxyanisole, ethoxyquin and disul-firam on acute pyrrolizidine alkaloid poisonings and mice. Res. Commun. Chem. Pathol. Pharmacol. 1982; 36: 341
  • Reddy B. S., Hirota N., Katayama S. Effect of dietary sodium ascorbate on 1,2-dimethylhydrazine-or methylnitrosourea-induced colon carcinogenesis in rats. Carcinogenesis 1982; 3: 1097
  • Shklar G. Oral mucosal carcinogenesis in hamsters: inhibition by vitamin E. J. Natl. Cancer Inst 1982; 68: 791
  • Reddy B. S., Maeura Y., Weisburger J. H. Effect of various levels of dietary butylated hydroxyanisole on methylazoxymethanol acetate-induced colon carcinogenesis in CF1 mice. J. Natl. Cancer Inst. 1983; 71: 1299
  • Williams G. M., Maeura Y., Weisburger J. H. Simultaneous inhibition of liver carcinogenicity and enhancement of bladder carcinogenicity of N-2-fluorenylacetamide by butylated hydroxytoluene. Cancer Lett. 1983; 19: 55
  • Reddy B. S., Maeura Y. Dose-response studies of the effect of dietary butylated hydroxyanisole on colon carcinogenesis induced by methylazoxymethanol acetate in female CFI mice. J. Natl. Cancer Inst. 1984; 72: 1181
  • Witschi H., Williamson D., Lock S. Enhancement of urethan tumorigenesis in mouse lung by butylated hydroxytoluene. J. Natl. Cancer Inst. 1977; 58: 301
  • Witschi H., Lock S. Enhancement of adenoma formation in mouse lung by butylated hydroxytoluene. Toxicol. Appl. Pharmacol. 1979; 50: 391
  • Cook M. G., McNamara P. Effect of dietary vitamin E on dimethylhydrazine-induced colonic tumors in mice. Cancer Res. 1980; 40: 1329
  • Witschi H. Enhancement of tumor formation in mouse lung by dietary butylated hydroxytoluene. Toxicology 1981; 21: 95
  • Djurhuns R., Lillehang J. R. Butylated hydroxytoluene: tumor-promoting activities in anin vitro two-stage carcinogenesis assay. Bull. Environ. Contam. Toxicol. 1982; 29: 115
  • Toth B., Patil K. Enhancing effect of vitamin E on murine intestinal tumorigenesis by 1,2-dimethylhydrazine dihydrochloride. J. Natl. Cancer Inst. 1983; 70: 1107
  • Maeura Y., Weisburger J. H., Williams G. M. Dose-dependent reduction of N-2-fluorenyla-cetamide-induced liver cancer and enhancement of bladder cancer in rats by butylated hydroxytoluene. Cancer Res. 1984; 44: 1604
  • Sugimura T., Fujiki H., Mori M., Nakayasu M., Terada M., Umezawa K., Moore R. E. Teleocidin: new naturally occurring tumor promoter. Carcinogenesis, a Comprehensive Survey, E. Hecker, N. E. Fusenig, W. Kunz, F. Marks, H. W. Thielmann. Raven Press, New York 1982; Vol. 7: 69
  • Sugimura T. Mutagens, carcinogens and tumor promoters in our daily food. Cancer 1982; 49: 1970
  • Ames B. N. Dietary carcinogens and anticarcinogens; oxygen radicals and degenerative diseases. Science 1983; 221: 1256
  • Sugimura T., Sato S. Mutagens-carcinogens in foods. Cancer Res. 1983; 43: 2415, Suppl
  • Berenblum I., Shubik P. A. A new quantitative approach to the study of the stages of chemical carcinogenesis in the mouse's skin. Br. J. Cancer 1947; 1: 383
  • Boutwell R. K. Some biological aspects of skin carcinogenesis. Proc. Exp. Tumor Res. 1964; 4: 207
  • Weinstein I. B., Troll W. National cancer institute workshop on tumor promotion and cofac-(ors in carcinogenesis. Cancer Res. 1977; 37: 3461
  • Hecker E. Structure activity relationships in diterpene esters irritant and cocarcinogenic to mouse skin. Carcinogenesis, Mechanism of Tumor Promotion and Cocarcinogenesis, T. J. Slaga, A. Sivak, R. K. Boutwell. Raven Press, New York 1978; Vol. 2: 11
  • Fujiki H., Mori M., Nakayasu M., Terada M., Sugimura T., Moore R. E. Indole alkaloids; dihydroteleocidin B, teleocidin and lyngbyatoxin A, as a new class of tumor promoters. Proc. Natl. Acad. Sci. U.S.A. 1980; 78: 3872
  • Fujiki H., Suganuma M., Nakayasu M., Hoshino H., Moore R. E., Sugimura T. The third class of new tumor promoters, polyacetates (debromoaplysiatoxin and aplysiatoxin), can differentiate biological actions relevant to tumor promoters. Gann 1982; 73: 495
  • Sugimura T. Potent tumor promoters other than phorbol ester and their significance. Gann 1982; 73: 499
  • Hicks R. M., Wakefield J., Chowaniec J. Evaluation of a new model to detect bladder carcinogens or co-carcinogens: results obtained with saccharin, cyclamate and cyclophosphamide. Chem. Biol. Interact. 1975; 11: 225
  • Cohen S. M., Arai M., Jacobs J. B., Friedell G. H. Promoting effect of saccharin and DL-tryptophan in urinary bladder carcinogenesis. Cancer Res. 1979; 39: 1207
  • Nakanishi K., Hagiwara A., Shibata M., Imaida K., Tatematsu M., Ito N. Dose-response of saccharin in induction of urinary bladder hyperplasias in Fischer 344 rats pretreated with N-butyl-N-(4-hydroxybutyl) nitrosamine. J. Natl. Cancer Inst. 1980; 65: 1005
  • Fukushima S., Friedell G. H., Jacobs J. B., Cohen S. M. Effect of L-tryptophan and sodium saccharin on urinary tract carcinogenesis initiated by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. Cancer Res. 1981; 41: 3100
  • Nakanishi K., Fukushima S., Hagiwara A., Tamano S., Ito N. Organ-specific promoting effects of phenobarbital sodium and sodium saccharin in the induction of liver and urinary bladder tumors in male F344 rats. J. Natl. Cancer Inst. 1982; 68: 497
  • Ito N., Fukushima S., Shirai T., Nakanishi K., Hasegawa R., Imaida K. Modifying factors in urinary bladder carcinogenesis. Environ. Health Perspect. 1983; 49: 217
  • Ito N., Fukushima S., Shirai T., Nakanishi K. Effects of promoters on N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder carcinogenesis in the rat. Environ. Health Perspect. 1983; 50: 61
  • Fukushima S., Hagiwara A., Ogiso T., Shibata M., Ito N. Promoting effects of various chemicals in rat urinary bladder carcinogenesis initiated by N-nitroso-n-butyl-(4-hydroxybutyl) amine. Food Chem. Toxicol. 1983; 21: 59
  • Peraino C., Fry R. J. M., Staffeldt E. Reduction and enhancement by phenobarbital of hepatocarcinogenesis induced in the rat by 2-acetylaminofluorene. Cancer Res. 1971; 31: 1506
  • Peraino C., Fry R. J. M., Staffeldt E., Christopher J. P. Enhancing effects of phenobarbitone and butylated hydroxytoluene on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat. Food Cosmet. Toxicol. 1977; 15: 93
  • Kitagawa T., Pitot H. C., Miller E. C., Miller J. A. Promotion by dietary phenobarbital of hepatocarcinogenesis by 2-methy-N, N-dimethyl-4-aminoazobenzene in the rat. Cancer Res. 1979; 39: 112
  • Ito N., Tatematsu M., Imaida K., Hasegawa R., Murasaki G. Effects of various promoters on the induction of hyperplastic nodules in rat liver. Gann 1980; 71: 415
  • Takano T., Tatematsu M., Hasegawa R., Imaida K., Ito N. Dose-response relationship for the promoting effect of phenobarbital on the induction of liver hyperplastic nodules in rats exposed to 2-fluorenylacetamide and carbon tetrachloride. Gann 1980; 71: 580
  • Ito N., Tsuda H., Hasegawa R., Imaida K. Comparison of the promoting effects of various agents in induction of preneoplastic lesions in rat liver. Environ. Health Perspect. 1983; 50: 131
  • Tsuda H., Fukushima S., Imaida K., Kurata Y., Ito N. Organ-specific promoting effect of phenobarbital and saccharin in induction of thyroid, liver, and urinary bladder tumors in rats after initiation with N-nitrosomethylurea. Cancer Res. 1983; 43: 3292
  • Hiasa Y., Ohshima M., Kitahori Y., Konishi N., Fujita T., Yuasa T. β-Cyclodextrin: promoting effect on the development of renal tubular cell tumors in rats treated with N-ethyl-N-hydroxyethylnitrosamine. J. Natl. Cancer Inst. 1983; 69: 963
  • Shirai T., Ohshima M., Masuda A., Tamano S., Ito N. Promotion of 2-(ethylnitrosamine) ethanol-induced renal carcinogenesis in rats by nephrotoxic compounds: positive responses with folic acid, basic lead acetate, and N-(3,5-dichlorophenyl) succinimide but not with 2,3-dibromo-1-propanol phosphate. J. Natl. Cancer Inst. 1984; 72: 477
  • Hiasa Y., Kitahori Y., Konishi N., Enoki N., Shimoyama T., Miyashiro A. Trisodium nitrilotriacetate monohydrate: promoting effects on the developing of renal tubular cell tumors in rats treated with N-ethyl-N-hydroxyethylnitrosamine. J. Natl. Cancer Inst. 1984; 72: 483
  • Ito N., Hagiwara A., Shibata M., Ogiso T., Fukushima S. Induction of squamous cell carcinoma in the forestomach of F344 rats treated with butylated hydroxyanisole. Gann 1982; 73: 332
  • Ito N., Fukushima S., Hagiwara A., Shibata M., Ogiso T. Carcinogenicity of butylated hydroxyanisole in F344 rats. J. Natl. Cancer Inst. 1983; 70: 343
  • Ishiwata H., unpublished data
  • Ishitani T., Hirata T., Takai G., Kimura S. Volatilization and decomposition of antioxidants by heating. Nippon Shokuhin Kogyo Gakkai-Shi 1976; 23: 244
  • Ishiwata H., Kaneko K., Kato S., Tanimura A. Decrease of butylated hydroxyanisole added in the diet for a carcinogenicity test in rats and mice. Bull. Environ. Contam. Toxicol. 1982; 28: 379
  • Ito N., Fukushima S., Imaida K., Sakata T., Masui T. Induction of papilloma in the forestomach of hamsters by butylated hydroxyanisole. Gann 1983; 74: 459
  • Ito N., Hirose M., Kurata Y., Ikawa E., Mera Y., Fukushima S. Induction of forestomach hyperplasia by crude butylated hydroxyanisole, a mixture of 3-tert and-2-tertisomers in Syrian golden hamsters is due to 3-tert-butylated hydroxyanisole. Gann 1984; 75: 471
  • Hirose M., Shibata M., Hagiwara A., Imaida K., Ito N. Chronic toxicity of butylated hydroxytoluene in Wistar rats. Food Cosmet. Toxicol. 1981; 19: 147
  • Shirai T., Hagiwara A., Kurata Y., Shibata M., Fukushima S., Ito N. Lack of carcinogenicity of butylated hydroxytoluene on long-term administration to B6C3F1 mice. Food Cosmet. Toxicol. 1982; 20: 861
  • Shirai T., Fukushima S., Ohshima M., Masuda A., Ito N. Effects of butylated hydroxyanisole, butylated hydroxytoluene, and NaCl on gastric carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine in F344 rats. J. Natl. Cancer Inst. 1984; 72: 1189
  • Hirayama T. Epidemiology of stomach cancer. Gann Monogr. 1971; 11: 3
  • Shirai T., Imaida K., Fukushima S., Hasegawa R., Tatematsu M., Ito N. Effect of NaCl, Tween 60 and a low dose of N'-ethyl-N'-nitro-N-nitrosoguanidine on gastric carcinogenesis of rat given a single dose of N-methyl-N'-nitro-N-nitrosoguanidine. Carcinogenesis 1982; 3: 1419
  • Takahashi M., Kokubo T., Furukawa F., Kurokawa Y., Tatematsu M., Hayashi Y. Effect of high salt diet on rat gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine. Gann 1983; 74: 28
  • Tatematsu M., Takahashi M., Fukushima S., Hananouchi M., Shirai T. Effects on rat of sodium chloride on experimental gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline-1-oxide. J. Natl. Cancer Inst. 1975; 55: 101
  • Tatematsu M., Takahashi M., Hananouchi M., Shirai T., Hirose M., Fukushima S., Ito N. Protective effect of mucin on experimental gastric cancer induced by N-methyl-N'-nitro-N-nitro-soguanidine plus sodium chloride in rat. Gann 1976; 67: 223
  • Takahashi M., Kokubo T., Furukawa F., Kurokawa Y., Hayashi Y. Promoting effects of sodium chloride, saccharin and others on experimental gastric carcinogenesis in the rat. Proc. Jpn. Cancer Assoc. 1983; 42: 87
  • Imaida K., Fukushima S., Shirai T., Ohtani M., Nakanishi K., Ito N. Promoting activities of butylated hydroxyanisole and butylated hydroxytoluene on 2-stage urinary bladder carcinogenesis and the inhibition of γ-glutamyl transpeptidase-positive foci development in the liver of rats. Carcinogenesis 1983; 4: 895
  • Ito N., Tatematsu M., Nakanishi K., Hasegawa R., Takano T., Imaida K., Ogiso T. The effects of various chemicals on the development of hyperplastic liver nodules in hepatectomized rats treated with N-nitrosodiethylamine or N-2-fluorenylacetamide. Gann 1980; 71: 832
  • Tamano S., Tsuda H., Tatematsu M., Hasegawa R., Imaida K., Ito N. Induction of γ-glutamyl transpeptidase positive foci in rat liver by pyrolysis products of amino acids. Gann 1981; 77: 747
  • Cameron R. G., Imaida K., Tsuda H., Ito N. Promotive effects of steroids and bile acids on hepatocarcinogenesis initiated by diethylnitrosamine. Cancer Res. 1982; 42: 2426
  • Ito N., Tsuda H., Hasegawa R., Imaida K. Sequential observation of pathomorphologic alterations in preneoplastic lesions during the promoting stage of hepatocarcinogenesis and the development of short-term test system for hepatopromoters and hepatocarcinogens. Toxicol. Pathol. 1982; 10: 37
  • Tamano S., Tsuda H., Fukushima S., Masui T., Hosoda K., Ito N. Dose and sex dependent effects of 2-acetylaminofluorene, 3′-methyl-4-dimethylaminoazobenzene and DL-ethionine in induction of γ-glutamyl transpeptidase-positive liver cell foci in rats. Cancer Lett. 1983; 20: 313
  • Tatematsu M., Hasegawa R., Imaida K., Tsuda H., Ito N. Survey of various chemicals for initiating and promoting activities in a short-termin vivo system based on generation of hyperplastic liver nodules in rats. Carcinogenesis 1983; 4: 381
  • Ito N., Tsuda H., Sakata T., Haasegawa R., Tamano S. Inhibitory effect of butylated hydroxyanisole and ethoxyquin on the induction of neoplastic lesions in rat liver after an initial treatment with N-ethyl-N-hydroxyethylnitrosamine. Gann 1983; 74: 466
  • Tsuda H., Sakata T., Tamano S., Okumura M., Ito N. Sequential observations on the appearance of neoplastic lesions in the liver and kidney after treatment with N-ethyl-N-hydroxyethyl-nitrosamine followed by partial hepatectomy and unilateral nephrectomy. Carcinogenesis 1983; 4: 523
  • Farber E. The pathology of experimental liver cell cancer. Liver Cell Cancer, D. A. Linsell, G. P. Warwich. Elsevier, Amsterdam 1976; 243
  • Bannasch P., Mayer D., Krech R. Neoplastische und präneoplastisch Veränderungen bei Ratten nach einmaliger oraler Applikation von N-nitrosomorpholin. J. Cancer Res. Clin. Oncol. 1979; 94: 233
  • Institute of Laboratory Animal Resources, National Research Council, National Academy of Sciences, Histologic typing of liver tumors of the rat. J. Natl. Cancer Inst. 1980; 64: 179
  • Fukushima S., Imaida K., Sakata T., Okumura T., Shibata M., Ito N. Promoting effects of sodium L-ascorbate on two-stage urinary bladder carcinogenesis in rats. Cancer Res. 1983; 43: 4454
  • Slaga T. J., Bowden J. D., Scribner J. D., Boutwell R. K. Dose-response studies on the ability of 7,12-dimethylbenz(alpha) anthracene and benz(alpha) anthracene to initiate skin tumors. J. Natl. Cancer Inst. 1974; 53: 1337
  • Tsuda H., Lee G., Farber E. Induction of resistant hepatocytes as a new principle for a possible short-termin vivo test for carcinogens. Cancer Res. 1980; 40: 1157
  • Fukushima S., Murasaki G., Hirose M., Nakanishi K., Hasegawa R., Ito N. Histopathological analysis of preneoplastic changes during N-butyl-N-(4-hydroxybutyl) nitrosamine induced urinary bladder carcinogenesis in rats. Acta Pathol. Jpn. 1982; 32: 243
  • Ito N., Matayoshi K., Arai M., Yoshioka Y., Kamanoto Y., Makiura S., Sugihara S. Effect of various factors on induction of urinary bladder tumors in animals by N-butyl-N-(4-hydrox-ybutyl) nitrosamine. Gann 1973; 64: 151
  • Ito N., Hiasa Y., Tamai A., Okajima E., Kitamura H. Histogenesis of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats. Gann 1969; 60: 401
  • Fukushima S., Kurata Y., Shibata M., Ikawa E., Ito N. Promotion by ascorbic acid, sodium erythorbate, and ethoxyquin of neoplastic lesions in rats initiated with N-butyl-N-(4-hydroxybu-tyl)nitrosamine. Cancer Lett. 1984; 23: 29
  • Fukushima S., Kurata Y., Shibata M., Ikawa E., Ito N. Promoting effect of sodium o-phenylphenate and o-phenylphenol on two-stage urinary bladder carcinogenesis in rats. Gann 1983; 74: 625
  • Masui T., Imaida K., Fukushima S., Shirai T., Hirose K., Ito N. Organ specificity of promotion effects by BHA, BHT and ascorbate in MNU initiated F344 rats, Froc. Jpn. Cancer Assoc. 1983; 42: 85
  • IARC Monogr. On Evaluation of Carcinogenic Risk of Chemicals to Man. International Agency for Research on Cancer, LyonFrance 1978; Vol. 17
  • Tsuda H., Sakata T., Shirai T., Kurata Y., Tamano S., Ito N. Modification of N-methyl-N-nitrosourea initiated carcinogenesis in the rat by subsequent treatment with antioxidants, pheno-barbital and ethinyl estradiol. Cancer Lett. 1984; 24: 19
  • Ishidate M., Odashima S. Chromosome tests with 134 compounds on Chinese hamster cellsin vitro—a screening for chemical carcinogens. Mutat. Res. 1977; 48: 337
  • Joner E. Butylhydroxyanisole (BHA), butylhydroxytoluene (BHT) and ethoxyquin (EMQ) tested for mutagenicity. Acta Vet. Scand. 1977; 18: 187
  • Annual Report of Cancer Research. National Cancer Center. Ministry of Health and Welfare of Japan, Tokyo 1979; 1111
  • Batzinger B. P., Ou S. Y. L., Bueding E. Antimutagenic effects of 2(3)-tert-butylhydroxyani-sole and of microbial agents. Cancer Res. 1978; 38: 4476
  • Cumming R. B., Walton M. F. Modification of the acute toxicity of mutagenic and carcinogenic chemicals in the mouse by prefeeding with antioxidants. Food Cosmet. Toxicol 1973; 11: 547
  • Shelef L. A., Chin B. Effect of phenolic antioxidants on the mutagenicity of aflatoxin B2. Appl. Environ. Microbiol. 1980; 40: 1039
  • Telford I. R., Woodruff C. S., Linford R. H. Fetal resorption in the rat as influenced by certain antioxidants. Am. J. Anat. 1962; 110: 29
  • Cleggy D. J. Absence of teratogenic effect of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) in rats and mice. Food Cosmet. Toxicol. 1965; 3: 387
  • Hansen E., Meyer O. A study of the teratogenicity of butylated hydroxyanisole on rabbits. Toxicology 1978; 10: 195
  • Vorhees C. V., Butcher R. E., Brunner R. L., Wootten V., Sabotka T. J. Developmental neurobehavioral toxicity of butylated hydroxyanisole (BHA) in rats. Neurobehav. Toxicol. Teratol 1981; 3: 321
  • Brown W. D., Johnson A. R., O'Halloran M. W. The effect of the level of dietary fat on the toxicity of phenolic antioxidants, Ausr. J. Exp. Biol. 1959; 37: 533
  • Creaven P. J., Davies W. H., Williams R. T. The effect of butylated hydroxytoluene, butylated hydroxyanisole and octyl gallate upon liver weight and biphenyl-4-hydroxylase activity in the rat. J. Pharm. Pharmacol. 1966; 18: 485
  • Martin A. D., Gilbert D. Enzyme changes accompanying liver enlargement in rats treated with 3-tert-butyl-4-hydroxyanisole. Biochem. J. 1968; 106: 22
  • Lam L. K. T., Wattenberg L. W. Effects of butylated hydroxyanisole on the metabolism of benzo[a]pyrene by mouse liver microsomes. J. Natl. Cancer Inst. 1979; 58: 413
  • Miranda C. L., Read R. L., Cheeke P. R., Buhler D. R. Protective effects of butylated hydroxyanisole against the acute toxicity of monocrotaline in mice. Toxicol. Appl. Pharmacol. 1981; 59: 424
  • Imaida K., Fukushima S., Shirai T., Masuda A., Hagiwara A., Ito N. Sequential analysis of BHA induced tumor development in F344 rats, Syrian golden hamsters and B6C3F1 mice. Proc. Jpn. Cancer Assoc. 1983; 42: 28
  • Lok E., Iverson F., Nera E. A., Clayson D. B. Studies on Effect of Butylated Hydroxyanisole (BHA) on Cell Proliferation in Rat Forestomach. Joint FAO/WHO Expert Committee on Food Additives. World Health Organization, Geneva 1983
  • Yokoro K. Carcinogenicity test of butylated hydroxyanisole. Annual Report of the Cancer Research. Ministry of Health and Welfare, Tokyo 1981; 1013
  • Assessment of evidence for carcinogenicity from studies in experimental animals. IARC Monogr. on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. International Agency for Research on Cancer, Lyon 1982; 12, Suppl. 4
  • Olsen P., Bille N., Meyer O. Hepatocellular neoplasms in rats induced by butylated hydroxytoluene (BHT). Acta Pharmacol. Toxicol. 1983; 53: 433
  • Wattenberg L. W. The role of the portal of entry in inhibition of tumorigenesis. Progress in Experimental Tumor Research, F. Homburger. S. Karger, Basel 1971; Vol. 14: 89
  • Wattenberg L. W. Inhibition of chemical carcinogenesis by antioxidants and some additional compounds. Fundamentals in Cancer Prevention, P. N. Magee, S. Takayama, T. Sugimura, T. Matsushima. University of Tokyo Press, Tokyo 1976; 153
  • Wattenberg L. W. Inhibitors of chemical carcinogenesis. Advances in Cancer Research, G. Klein, S. Weinhouse. Academic Press, New York 1978; Vol. 26: 197
  • Richardson H. L., Stier A. R., Borsoo-Nachtenbel E. Liver tumor inhibition and adrenal histological responses in rats to which 3′-methyl-4-dimethylaminoazobenzene and 20-methylcholan-threne were simultaneously administered. Cancer Res. 1952; 12: 356
  • Miller E. C., Miller J. A., Brown R. R., MacDonald J. On the protective action of certain polycyclic aromatic hydrocarbons against carcinogenesis by aminoazodyes and 2-acetylaminofluor-ene. Cancer Res. 1958; 18: 469
  • Marugami M., Ito N., Konishi Y., Hiasa Y., Farber E. Influence of 3-methylcholanthrene on liver carcinogenesis in rats ingesting DL-ethionin, 3′-methyl-4-dimethylaminoazobenzene and N-2-fluorenylacetamide. Cancer Res. 1967; 27: 2011
  • Makiura S., Aoe H., Sugihara S., Hirao K., Arai M., Ito N. Inhibitory effect of polychlor-inated biphenyls on liver tumorigenesis in rats treated with 3′-methyl-4-dimethylaminoazobenzene, N-2-fluorenylacetamide, and diethylnitrosamine. J. Natl. Cancer Inst. 1974; 53: 1253
  • Speier J. L., Wattenberg L. W. Alterations in microsomal metabolism of benzo[a]pyrene in mice fed butylated hydroxyanisole. J. Natl. Cancer Inst. 1975; 55: 469
  • Benson A. M., Batzinger R. P., Ou S. Y.-L., Bueding E., Cha Y.-N., Talalay P. Elevation of hepatic glutathione S-transferase activities and protection against metabolites of benzo[a]pyrene by dietary antioxidants. Cancer Res. 1978; 38: 4486
  • Cha Y.-N., Martz F., Bueding E. Enhancement of liver microsome epoxide hydratase activity in rodents by treatment with 2(3)-tert-butyl-4-hydroxyanisole. Cancer Res. 1978; 38: 4496
  • Kahi R., Wulff U. Induction of rat hepatic epoxide hydratase by dietary antioxidants. Toxicol. Appl. Pharmacol. 1978; 47: 217
  • Benson A. M., Cha Y.-N., Bueding E., Heine H. S., Talalay P. Evaluation of extrahepatic glutathione S-transferase and epoxide hydratase activities by 2(3)-tert-butyl-4-hydroxyanisole. Cancer Res. 1979; 39: 2971
  • Cha Y.-N., Heine H. S. Comparative effects of dietary administration of 2(3)-tert-4-hydroxy-anisole and 3,5-di-tert-butyl-4-hydroxytoluene on several hepatic enzyme activities in mice and rats. Cancer Res. 1982; 42: 2609
  • Sparnins V. L., Venegas P. L., Wattenberg L. W. Glutathione S-transferase activity: enhancement by compounds inhibiting chemical carcinogenesis and by dietary constituents. J. Natl. Cancer Inst. 1982; 68: 493
  • Narisawa T., Magandia N. E., Weisburger J. H., Wynder E. L. Promoting effects of bile acids on colon carcinogenesis after intrarectal instillation of N-methyl-N'-nitro-N-nitrosoguanidine in rats. J. Natl. Cancer Inst. 1974; 53: 1093
  • Hirose M., Shirai T., Tsuda H., Fukushima S., Ogiso T., Ito N. Effect of phenobarbital, polychlorinated biphenyl and sodium saccharin on hepatic and renal carcinogenesis in unilaterally nephrectomized rats given N-ethyl-N-hydroxyethylnitrosamine orally. Carcinogenesis 1981; 2: 1299
  • Hiasa Y., Kitahori Y., Ohshima M., Fujita T., Yuasa T., Konishi N., Miyashiro A. Promoting effects of phenobarbital and barbital on development of thyroid tumors in rats treated with N-bis(2-hydroxypropyl)nitrosamine. Carcinogenesis 1982; 3: 1187
  • Hiasa Y., Kitahori Y., Enoki N., Konishi M., Shinoyama T. 4,4′-Diaminodiphenylmethane: promoting effect on development of thyroid tumors in rats treated with N-bis(2-hydroxypro-pyl)nitrosamine. J. Natl. Cancer Inst. 1984; 72: 471
  • Fukushima S., Hirose M., Hagiwara A., Hasegawa R., Ito N. Inhibitory effect of 4,4′-diaminodiphenylmethane on liver, kidney and bladder carcinogenesis in rats ingesting N-ethyl-N-hydroxyethylnitrosamine or N-butyl-N-(4-hydroxybutyl)nitrosamine. Carcinogenesis 1981; 2: 1033
  • Søndergaaed D., Olsen P. The effect of butylated hydroxytoluene (BHT) on the rat thyroid. Toxicol. Lett. 1982; 10: 239

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