Abstract
In the mind of the lay and even professional public, cancer of various types has been considered to be a “spontaneous” condition (Weisburger, 1973a). The concept that some types of cancer might, however, be caused by environmental factors traces back to the observation of Pott in the late eighteenth century that human scrotal cancer in Great Britain was associated with the occupation of his patients, namely sweeping chimneys. Since that time, people in other occupations have been demonstrated to have certain risks of developing cancer at some sites. Overall, however, occupational cancers are relatively rare events which affect only limited numbers of individuals. The bulk of human cancers were until recently considered to stem from unknown elements. It was a consideration of international incidence rates of various types of cancer, and the fact that the incidence depends in part on the site of residence, which underwrote the concept that many types of human cancer are caused, mediated, or modified by environmental factors (Wynder and Mabuchi, 1972; Higginson and Muir, 1973). Thus examination of the incidence of two types of cancer of the digestive tract, namely stomach cancer and large bowel cancer, in populations in Europe, Latin America, Japan, and the North American continent indicated clearly that they have quite different causative and modifying elements, but both are associated mainly with dietary factors. Lung cancer, on the other hand, has been definitely traced to the personal habit of smoking cigarettes.
Supported in part by Grants CA 12376, CA 14298, and CA 15400 and Contract CP 43378 from the National Cancer Institute, NIH, U.S. Public Health Service.
Supported in part by Grant BC-133 from the American Cancer Society.
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References
Alarif, A., and Epstein, S. S., 1974, The metabolism of the pancreatic carcinogens N-14C-methyl-N- nitrosourethane and methylnitrosourea in guinea pigs, and their in vitro metabolism in the guinea pig and human pancreas, Proc. Am. Assoc. Cancer Res. 15: 68.
Albrecht, R., and Manchon, P., 1973, Metabolisme et toxicité des colorants azoiques, Ann. Nutr. Aliment. 27: 1–9.
Althoff, J., Krueger, F. W., and Mohr, U., 1973, Carcinogenic effect of dipropylnitrosamine and compounds related by β-oxidation, J. Natl. Cancer Inst. 51: 287–288.
Ames, B. N., Sims, P., and Grover, P. L., 1972, Epoxides of carcinogenic polycyclic hydrocarbons are frameshift mutagens. Science 176: 47–49.
Ames, B. N., Durston, W. E., Yamasaki, E., and Lee, F. D., 1973a, Carcinogens are mutagens: A simple test system combining liver homogenates for activation and bacteria for detection, Proc. Natl. Acad. Sci. 70: 2281–2285.
Ames, B. N., Lee, F. D., and Durston, W. E., 1973b, An improved bacterial test system for the detection and classification of mutagens and carcinogens, Proc. Natl. Acad. Sci. 70: 782–786.
Arcos, J. C. and Argus, M. F., 1974, Chemical Induction of Cancer, Academic Press, New York and London.
Argus, M. F., Sohal, R. S., Bryant, G. M., Hoch-Ligeti, C., and Arcos, J. C., 1973, Dose-response and ultrastructural alterations in dioxane carcinogenesis, Europ. J. Cancer 9: 237–243.
Baird, W. M., Dipple, A., Grover, P. L., Sims, P. and Brookes, P., 1973, Studies on the formation of hydrocarbon-deoxyribonucleoside products by the binding of derivatives of 7-methylbenz(a)anthracene to DNA in aqueous solution and in mouse embryo cells in culture. Cancer Research 33: 2386–2392.
Bartsch, H., and Hecker, E., 1971, On the metabolic activation of the carcinogen N-hydroxy-N-2- acetylaminofluorene. IIL Oxidation with horseradish peroxidase to yield 2-nitrosofluorene and N-acetoxy-N-2-acetylaminofluorene, Biochim. Biophys. Acta 237: 567.
Bartsch, H., Miller, J. A., and Miller, E. C., 1972, N-Acetoxy-N-acetylaminoarenes and nitro- soarenes: One-electron non-enzymatic and enzymatic oxidation products of various carcinogenic aromatic acetylhydroxamic acids, Biochim. Biophys. Acta 273: 40.
Bartsch, H., Dworkin, C., Miller, E. C., and Miller, J. A., 1973, Formation of electrophilic N-acetoxyarylamines in cytosols from rat mammary gland and other tissues by transacetylation from the carcinogen N-hydroxy-4-acetylaminobipheryl, Biochim. Biophys. Acta 304: 42–55.
Bast, R. C., Jr., Shears, B. W., Rapp, H. J., and Gelboin, H. V., 1973, Aryl hydrocarbon (benzo(a)pyrene) hydroxylase in guinea pig peritoneal macrophages: Benz(a)anthracene-induced increase of enzyme activity in vivo and in cell culture, J. Natl. Cancer Inst. 51: 675–678.
Becking, G. C., 1973, Vitamin A status and hepatic drug metabolism in the rat, Canad. J. Physiol. Pharmacol. 51: 6–11.
Belitsky, G. A., and Yaguzhinsky, L. S., 1972, The effect of benz(a)anthracene as an inductor of multipurpose oxidases on the toxic and antiblastomic action of N,N-bis(chloroethyl)aniline, Voprosy Onkol. 18 (6): 72–74.
Berenblum, L, 1969, A re-evaluation of the concept of cocarcinogenesis. Prog. Exp. Tumor Res. 2: 21–30.
Bergmann, E. D., and Pullman, B., eds., 1969, Physicochemical Mechanism of Carcinogenesis, Israel Academy of Sciences and Humanities, Jerusalem.
Blattmann, L., and Preussmann, R., 1973, Struktur von metaboliten Carcinogener Dialkylni- trosamine im Rattenurin, Z. Krebsforsch. 79: 3–5.
Bogovski, P., Preussmann, R., Walker, E. A., and Davis, W., eds., 1972, N-Nitroso Compounds: Analysis and Formation, Sciendfic Publication No. 3, International Agency for Research on Cancer, Lyon.
Booth, J., Keysell, G. R., and Sims, P., 1973, Formation of glutathione conjugates as metabolites of 7,12-dimethylbenz(a)anthracene by rat liver homogenates, Biochem. Pharmacol. 22: 1781–1791.
Booth, J., Keysell, G. R., and Sims, P., 1974, Effect of oestradiol on the in vitro metabolism of 7,12-dimethylbenz(a)anthracene and its hydroxymethyl derivadves, Biochem. Pharmacol. 23: 735–744.
Borchert, P., Wislocki, P. G., Miller, J. A., and Miller, E. C., 1973a, The metabolism of the naturally occurring hepatocarcinogen safrole to I’-hydroxysafrole and the electrophilic reactivity of I’-acetoxysafrole, Cancer Res. 33: 575–589.
Borchert, P., Miller, J. A., Miller, E. G., and Laires, T. K., 19736, l’-Hydroxysafrole: A proximate carcinogenic metabolite of safrole in the rat and mouse. Cancer Res. 33: 590–600.
Boutwell, R. K., 1974, The function and mechanism of promoters of carcinogenesis, CRC Crit. Rev. Toxicol. 2: 419–443.
Boyd, J. S., and Smellie, R. M. S., eds., 1972, Biological Hydroxylation Mechanisms, Academic Press, New York.
Boyland, E., 1952, Different types of carcinogens and their possible modes of action. Cancer Res. 12: 77–84.
Boyland, E., 1971, Mercapturic acid conjugation, in: Concepts in Chemical Pharmacology, Part II ( B. B. Brodie and J. R. Gillette, eds.), pp. 401–421, Springer, New York.
Bralow, S. P., Gruenstein, M., and Meranze, D. R., 1973, Host resistance to gastric adenocar- cinomatosis in three strains of rats ingesting N-methyl-N-nitro-N-nitrosoguanidine, Oncology 27: 168.
Brodie, B. B., and Gillette, J. R., eds., 1971, Concepts in Chemical Pharmacology, Part II, Springer, New York.
Brown, J. B., 1968, Purine N-oxides as antimetabolites and oncogens, in: Frontiers of Biology, Vol. 10, pp. 237–259, North-Holland, Amsterdam.
Bürkl, K., Liebelt, A. G., and Bresnick, E., 1973, Expression of aryl hydrocarbon hydroxylase induction in mouse tissues in vivo and in organ culture, Arch. Biochem. Biophys. 158: 641–649.
Calder, I. C., Creek, M. J., and Williams, P. J., 1974, N-Hydroxyphenacetin as a precursor of 3-substituted 4-hydroxyacetanilide metabolites of phenacetin, Chem.-Biol. Interact. 8: 87–90.
Campbell, T. G., Caedo, J. P., Jr., Bulatao-Jayme, J., Salamat, L., and Engel, R. W., 1970, Aflatoxin M1 in human urine. Nature (Loud.) 227: 403.
Cardesa, A., Pour, P., Rustia, M., Althoff, J., and Mohr, U., 1973, The syncarcinogenic effect of methylcholanthrene and dimethylnitrosamine in Swiss mice, Z. Krebsforsch. 79: 98–107.
Chan, P. G., and Cohen, L. A., 1974, Effect of dietary fat, antiestrogen, and antiprolactin on the development of mammary tumors in rats, J. Natl. Cancer Inst. 52: 25–30.
Chan, P. G., Okamoto, T., and Wynder, E. L., 1972, Possible role of riboflavin deficiency in epithelial neoplasia. III. Induction of microsomal aryl hydrocarbon hydroxylase, J. Natl. Cancer Inst. 48: 1341–1345.
Clayson, D. B., 1962, Chemical Carcinogenesis, Litde, Brown, Boston.
Cohen, S. M., Alter, A., and Bryan, G. T., 1973, Distribution of radioactivity and metabolism of formic acid 2-(4-(5-nitro-2-furyl)-2-14C-2-thiazolyl) hydrazide following oral administration of rats and mice. Cancer Res. 33: 2802–2809.
Conney, A. H., 1967, Pharmacological implications of microsomal enzyme induction, Pharmacol. Rev. 19: 317–366.
Conney, A. H., 1973, Carcinogen metabolism and human cancer, New Engl. J. Med. 289: 971–973.
Conney, A. H., and Burns, J. J., 1972, Metabolic interactions among environmental chemicals and drugs, Science 178: 576–586.
Conney, A. H., and Kuntzman, R., 1971, Metabolism of normal body constituents by drug metabolizing enzymes in liver microsomes, in: Concepts in Chemical Pharmacology, Part 2 ( B. B. Brodie and J. R. Gillette, eds.), pp. 401–421, Springer, New York.
Conney, A. H., Levin, W., Jacobson, M., and Kuntzman, R., 1973, Effect of drugs and environmental chemicals on steroid metabolism, Clin. Pharmacol. Ther. 14: 727–741.
Cornish, H. H., Ling, B. P., and Barth, M. L., 1973, Phenobarbital and organic solvent toxicity. Am. Ind. Hyg. Assoc. J. 34: 487–492.
Craddock, V. M., 1971, Liver carcinomas induced in rats by single administration of dimethylni-trosamine after partial hepatectomy, J. Natl. Cancer Inst. 47: 889–907.
Czygan, P., Greim, H., Garro, A. J., Hutterer, F., Schaffner, F., Popper, H., Rosenthal, O., and Cooper, D. Y., 1973, Microsomal metabolism of dimethylnitrosamine and the cytochrome P-450 dependency of its activation to a mutagen, Cancer Res. 33: 2983–2986.
Czygan, P., Greim, H., Garro, A., Schaffner, F., and Popper, H., 1974, The effect of dietary protein deficiency on the ability of isolated hepatic microsomes to alter the mutagenicity of a primary and a secondary carcinogen. Cancer Res. 34: 119–123.
Dalezios, J., Wogan, G. N., and Weinreb, S. M., 1971, Aflatoxin P1: A new aflatoxin metabolite in monkeys. Science 171: 584–585.
Daly, J., 1971, Enzymatic oxidation at carbon, in: Concepts in Chemical Pharmacology, Part II ( B. B. Brodie and J. R. Gillette, eds.), pp. 285–311, Springer, New York.
Dao, T. L. and Libby, P. R., 1972, Steroid sulphate formation in human breast tumors and hormone dependency, in: Estrogen Target Tissues and Neoplasia ( T. L. Dao, ed.), pp. 181–200, Chicago University Press, Chicago.
Diamond, L., and Gelboin, H. V., 1969, Alpha-naphthoflavone: An inhibitor of hydrocarbon cytotoxicity and microsomal hydroxylase. Science 7: 1023–1025.
DiLuzio, N. R., Stege, T. E., and Hoffman, E. O., 1973, Protective influence of diphenyl-p-phenylenediamine on hydrazine induced lipid peroxidation and hepatic injury, Exp. Mol. Pathol. 19: 284–292.
DiPaolo, J. A., Nelson, R. L., Donovan, P. J., and Evans, C. H., 1973, Host-mediated in vivo-in vitro assay for chemical carcinogenesis, Arch. Pathol. 95: 380–385.
Dipple, A., and Slade, T. A., 1970, Structure and activity in chemical carcinogenesis: Reactivity and carcinogenicity of 7-bromomethylbenz(a)anthracene and 7-bromomethyl-12-methyl- benz(a)anthracene, Europ. J. Cancer 6: 417–423.
Domsky, I. I, Lijinsky, W., Spencer, K., and Shubik, P., 1963, Rate of metabolism of 9,10-dimethyl- 1,2-benzanthracene in newborn and adult mice, Proc. Soc. Exp. Biol. Med. 113: 110–112.
Druckrey, H., 1973, Specific carcinogenic and teratogenic effects of “indirect” alkylating methyl and ethyl compounds, and their dependency on stages of ontogenic developments, Xenobiotica 3: 271–303.
Druckrey, H., Preussmann, R., Ivankovic, S., Schmidt, C. H., Mennel, H. D., and Stahl, K. W., 1964, Selektive Erzeugung von Blasenkrebs an Ratten durch Dibutyl- und N-Butyl-N-butanol(4)-nitrosamin, Z. Krebsforsch. 66: 280.
Druckrey, H., Ivankovic, S., Bücheler, J., Preussmann, R., and Thomas, C., 1968, Erzeugung von Magen- und Pankreas-Krebs beim Meerschweinchen durch Methylnitrosoharnstoff und-urethan, Z. Krebsforsch 71: 167–182.
Duncan, M. E., and Brookes, P., 1973, The induction of azaguanine-resistant mutants in cultured Chinese hamster cells by reactive derivatives of carcinogenic hydrocarbons. Mutation Res. 21: 107–118.
Durston, W. E. and Ames, B. N., 1974, A simple method for the detection of mutagens in urine studies with the carcinogen 2-acetylaminofluorene, Proc. Natl. Acad. Sci. 71: 737–741.
Endo, H., and Takahashi, K., 1973, Methylguanidine, a naturally occurring compound showing mutagenicity after nitrosation in gastric juice. Nature (Lond.) 245: 325–326.
Endo, H., Ono, T., and Sugimura, T., eds., 1971, Chemistry and Biological Actions of 4-Nitroquinoline-l- oxide. Springer, New York.
Fahrig, R., 1973, Metabolic activation of mutagens in mammals: Host-mediated assay utilizing the induction of mitotic gene conversion in Saccharomyces cerevisiae, Agents Actions 3: 99–110.
Farber, E., 1973a, Hyperplasticliver nodules, in: Methods in Cancer Research, Vol. VII, Aczidemic Press, New York.
Farber, E., 19736, Carcinogenesis—Cellular evolution as a unifying thread. Cancer Res. 33: 2537–2550.
Fischer, L. J., Kent, J. H., and Weissinger, J. L., 1973, Absorption of diethylstilbestrol and its glucuronide conjugate from the intestine of five- and twenty-five-day-old rats, J. Pharmacol. Exp. Ther. 185: 163–170.
Fishman, W. H., 1970, Metabolic Conjugation and Metabolic Hydrolysis, Vols. I and I I, Academic Press, New York.
Fiume, L., Campadelli-Fiume, G., Magee, P. N., and Holsman, J., 1970, Cellular injury and carcinogenesis: Inhibition of metabolism of dimethylnitrosamine by aminoacetonitrile, Biochem. J. 120: 601–605.
Fowler, J. S. L., 1969, Carbon tetrachloride metabolism in the rabbit, Brit. J. Pharmacol. 37: 733–737.
Franchi, G., Forgione, A., Filippeschi, S., Csetenyi, J., and Garattini, S., 1973, A spectrophotometric method for the estimation of the carcinostatic agent 6-chrysenamine (F.O.R.T.C. 116) in biological fluids and tissues, Europ. J. Cancer 9: 591–595.
Fukuda, S., and Yamamoto, N., 1972, Detection of activating enzymes for 4-nitroquinoline-L-oxide activation with a microbial assay system. Cancer Res. 32: 735–439.
Gabaldon, M., and Lacomba, J., 1972, Glucuronyltransferase activity towards diethylstilbestrol in rat and hamster: Effect of activators, Europ. J. Cancer 8: 275–279.
Gandolfi, A. J., and Van Dyke, R. A., 1973, Dechlorination of chloroethane with a reconstituted liver microsomal system, Biochem. Biophys. Res. Commun. 53: 687–692.
Garner, R. C., 1973, Chemical evidence for the formation of a reactive aflatoxin Bi metabolite by hamster liver microsomes, FEBS Letters 36: 261–264.
Garner, R. C., Miller, E. C., Miller, J. A., Garner, J. V., and Hamson, R. S., 1971, Formation of a factor lethal for S. typhimurium TA 1530 and TA 1531 on incubation of aflatoxin B1 with rat liver microsomes, Biochem. Biophys. Res. Commun. 45: 774–780.
Gelboin, H. V., 1969, A microsome-dependent binding of benzo(a)pyrene to DNA, Cancer Res. 29: 1272–1276.
Gelboin, H. V., Kinoshita, N., and Wiebel, F. J., 1972; Microsomal hydroxylases: Induction and role in polycyclic hydrocarbon carcinogenesis and toxicity. Fed. Proc. 31: 1298–1309.
Genta, V. M., Kaufman, D. G., Harris, C. C., Smith, J. M., Sporn, M. B., and Saffiotti, U., 1974, Vitamin A deficiency enhances binding of benzo(a)pyrene to tracheal epithelial DNA, Nature(Lond.) 247: 48–49.
Gielen, J. E., and Nebert, D. W., 1971, Microsomal hydroxylase induction in liver cell culture by phenobarbital, polycyclic hydrocarbons and p,p′-DDT, Science 172: 167–169.
Gillette, J. R., 1971, Reductive enzymes, in: Concepts in Biochemical Pharmacology, Part 2 ( B. B. Brodie and J. R. Gillette, eds.), pp. 349–361, Springer, New York.
Gillette, J. R., Menard, R. H., and Stripp, B., 1973, Active products of fetal drug metabolism, Clin. Pharmacol. Ther. 14: 680–692.
Gingell, R., and Bridges, J. W., 1973, Intestinal azo-reduction and glucuronide conjugation of prontosil, Xenobiotica 3: 599–604.
Gingell, R., Bridges, J. W., and Williams, R. T., 1971, The role of the gut flora in the metabolism of prontosil and neoprontosil in the rat, Xenobiotica 1: 143–156.
Ginter, E., 1973, Cholesterol: Vitamin C controls its transformation to bile acids. Science 1791: 702–704.
Gorrod, J. W., 1973, Differentiation of various types of biological oxidation of nitrogen in organic compounds, Chem.-Biol. Interact. 7: 289–303.
Goth, R. and Rajewsky, M. F., 1972, Ethylation of nucleic acids by ethylnitrosourea-L-14C in the fetal and adult rat. Cancer Res. 32: 1501–1505.
Gram, T. E., 1973, Comparative aspects of mixed function oxidation by lung and liver of rabbits. Drug Metab. Rev. 2: 1–32.
Grantham, P. H., Weisburger, J. H., and Weisburger, E. K., 1973, Effect of the antioxidant butylated hydroxytoluene (BHT) on the metabolism of the carcinogens N-2-fluorenylacetamide and iV-hydroxy-N-2-fluorenylacetamide, Food Cosmet. Toxicol. 11: 209–217.
Grantham, P. H., Giao, Ng. B., Mohan, L. C., Weisburger, E. K., Buu-Hoi, Ng. P., and Roncucci, R., 1974a, Metabolism of 6-aminochrysene in the rat, Toxicol. Appl. Pharmacol. 29: 95.
Grantham, P. H., Mohan, L. C., Weisburger, E. K., Fales, H. M., Sokoloski, E. A., and Weisburger, J. H., 1974b, Identification of new water soluble metabolites of acetanilide, Xenobiotica 4: 69–76.
Grover, P. L., and Sims, P., 1968, Enzyme-catalysed reaction of polycyclic hydrocarbons with deoxyribonucleic acid and protein in vitro, Biochem. J. 110: 159–160.
Grover, P. L., Hewer, A., and Sims, P., 1973, K-region epoxides of polycyclic hydrocarbons: Formation and further metabolism of benz(a)anthracene-5,6-oxide by human lung preparations, FEBS Letters 34: 63–68.
Gutmann, H. R., 1974, Isolation and identification of the carcinogen N-hydroxy-2- fluorenylacetamide and related compound by liquid chromatography, Anal. Biochem. 58: 469–478.
Gutmann, H. R., Galitski, S. B., and Foley, W. A., 1967, The conversion of noncarcinogenic aromatic amides to carcinogenic arylhydroxamic acids by synthetic N-hydroxylation, Cancer Res. 27: 1443–1455.
Gutmann, H. R., Malejka-Giganti, D., Barry, E. J., and Rydell, R. C., 1972, On the correlation between the hepatocarcinogenicity of the carcinogen N-2-fluorenylacetamine and the metabolic activation by the rat. Cancer Res. 32: 1554–1561.
Hadjiolov, D., 1971, The inhibition of dimethylnitrosamine carcinogenesis in rat liver by aminoacetonitrile, Z. Krebsforsch. 76: 91–92.
Harris, P. N., Gibson, W. R., and Dillard, R. D., 1970, The oncogenicity of two l,l-diaryl-2- propynyl-N-cycloalkylcarbamates, Cancer Res. 30: 2952–2954.
Hathway, D. E., 1970, Foreign Compound Metabolism in Mammals, Vol. I, The Chemical Society, Burlington House, London.
Hathway, D. E., 1972, Foreign Compound Metabolism in Mammals, Vol. II, The Chemical Society, Burlington House, London.
Hecker, E., 1971, Isolation and characterization of cocarcinogenic principles from croton oil, in: Methods in Cancer Research ( H. Busch, ed.) Vol. 6, pp. 439–484, Academic Press, New York.
Heidelberger, C., 1973, Current trends in chemical carcinogenesis. Fed. Proc. 32: 2154–2161.
Higginson, J. and Muir, C. S., 1973, Epidemiology, in: Cancer Medicine ( J. F. Holland and E. Frei, III, eds.), pp. 241–306, Lea and Febiger, Philadelphia.
Hill, M. J., 1974, Bacteria and the etiology of colonic cancer, Cancer 34: 815–818.
Hill, D. L. and Shih, T. W., 1974, Vitamin A compounds and analogs as inhibitors of mixed function oxidases that metabolize carcinogenic polycyclic hydrocarbons and other compounds. Cancer Res. 34: 564–570.
Hill, M. J. and Aries, V. C., 1971, Faecal steroid composition and its relationship to cancer of the large bowel, J. Pathol. 104: 129–139.
Hill, M. J., Drasar, B. S., Aries, V., Crowther, J. S., Hawksworth, G., and Williams, R. E. O., 1971, Bacteria and aetiology of cancer of large bowel, Lancet 1: 95–100.
Hoch-Ligeti, C., Argus, M. F., and Arcos, J. C., 1968, Combined carcinogenic effects of dimethylnitrosamine and 3-methylcholanthrene in the rat, J. Natl. Cancer Inst. 40: 535–549.
Hoffmann, D., and Wynder, E. L., 1971, A study of tobacco carcinogenesis. XL Tumor initiators, tumor accelerators and tumor promoting activity of condensate fractions. Cancer 27: 848–864.
Hollaender, A., ed., 1971, Chemical Mutagens: Principles and Methods for Their Detection, Plenum Press, New York.
Hsu, I. C., Shumaker, R. C., and Allen, J. R., 1973, Tissue distribution of tritum-labeled dehydroretronecine, Chem.-Biol. Interact. 8: 163–170.
Huberman, E., and Sachs, L., 1973, Metabolism of the carcinogenic hydrocarbon benzo(a)pyrene in human fibroblast and epithelial cells. Int. J. Cancer 11: 412–418.
Hucker, H. B., 1970, Species differences in drug metabolism, Ann. Rev. Biochem. 10: 99–118.
Hucker, H. B., 1973, Intermediates in drug metabolism reaction. Drug Metab. Rev. 21: 33–56.
Hustad, G. O., Cerveny, J. G., Trenk, H., Deibel, R. H., Kaulter, D. A., Fazio, T., Johnston, R. W., and Kolari, O. E., 1973, Effect of sodium nitrite and sodium nitrate on botulinal toxin production and nitrosamine formation in wieners, Appl. Microbiol. 26: 22–26.
IARC Monograph No. 4 on the Evaluation of Carcinogenic Risk of Chemicals to Man, 1974, International Agency for Research on Cancer, Lyon.
IARC Monograph No. 5 on the Evaluation of Carcinogenic Risk of Chemicals to Man, 1974, International Agency for Research on Cancer, Lyon.
Ilett, K. F., Reid, W. D., Sipes, I. G., and Krishna, G., 1973, Chloroform toxicity in mice: Correlation of renal and hepatic necrosis with covalent binding of metabolites to tissue macromolecules, Exp. Mol. Pathol. 19: 215–229.
Imamura, T., and Ikeda, M., 1973, Lower fiducial limit of urinary metabolite level as an index of excessive exposure to industrial chemicals, Brit. J. Ind. Med. 30: 289–292.
Irving, C. C., 1970, Conjugates of N-hydroxy compounds, in: Metabolic Conjugation and Metabolic Hydrolysis, Vol. I, ( W. H. Fishman, ed.), pp. 53–119, Academic Press, New York.
Ito, N., Hiasa, Y., Toyoshima, K., Okajima, E., Kamamoto, Y., Makiura, S., Yokota, Y., Sugihara, S., and Matayoshi, K., 1973, Rat bladder tumors induced by N-butyl-N-(4- hydroxybutyl)nitrosamine, in: Topics in Chemical Carcinogenesis ( W. Nakahara, S. Takayama, T. Sugimura, and S. Odashima, eds.), p. 175, University Park Press, Baltimore.
Jago, M. V., Edgar, J. A., Smith, L. W., and Culvenor, C. C. J., 1970, Metabolic conversion of heliotridine-based pyrrolizidine alkaloids to dehydroheliotridine, Mol Pharmacol. 6: 402–406.
Janss, D. H., Moon, R. C., and Irving, C. C., 1972, The binding of 7,12-dimethylbenz(II)anthracene to mammary parenchyma DNA and protein in vivo, Cancer Res. 32: 254–258.
Jerina, D. M. and Daly, J. W., 1974, Arene oxides: A new aspect of drug metabolism. Science 185: 573–582.
Jones, A. R., and Edwards, K., 1973, Alkylating esters. VII. The metabolism of iso-propyl methanesulphonate and iso-propyl iodide in the rat, Experientia 29: 538–539.
Juchau, M. R., Zachariah, P. K., Colson, J., Symms, K. G., Kramer, J., and Jaffe, S. J., 1974, Studies on human placental carbon monoxide-binding cytochrome. Drug Metab. Disposition 2: 79–86.
Kamataki, J., Kitada, M., and Kitagawa, H., 1973, Difference in the substrate specificities of drug metabolizing enzymes in human term placenta and fetal liver, Chem. Pharm. Bull. 21: 2329–2331.
Kato, R., Shoji, H., and Takanaka, A., 1967, Metabolism of carcinogenic compounds. I. Effect of phénobarbital and methylcholanthrene on the activities of N-demethylation of carcinogenic compounds by liver microsomes of male and female rats, Gann 58: 467–469.
Kaufman, D. G., Genta, V. M., Harris, C. C., Smith, J. M., Sporn, M. B., and Saffiotti, U., 1973, Binding of 3H-labeled benzo(a)pyrene to DNA in hamster trachea epithelial cells. Cancer Res. 33: 2837–2841.
Kawachi, T., Kogure, K., Kamijo, Y., and Sugimura, T., 1970, The metabolism of N-methyl-N′- nitro-N-nitrosoguanidine in rats, Biochim. Biophys. Acta 222: 409–415.
Keefer, L. K., Lijinsky, W., and Gargia, H., 1973, Deuterium isotope effect on the carcinogenicity of dimethylnitrosamine in rat liver, J. Natl. Cancer Inst. 51: 299–302.
Keightly, D. D., and Okey, A. B., 1973, Effects of dimethylbenz(a)anthracene and dihydrotestos- terone on estradiol-17β binding in rat mammary cytosol fraction. Cancer Res. 33: 2637–2642.
Kellermann, G., Shaw, C. R., and Luyten-Kellermann, M., 1973a, Aryl hydrocarbon hydroxylase inducibility and bronchogenic carcinoma, N. Engl. J. Med. 289: 934–937.
Kellermann, G., Luyten-Kellermann, M., and Shaw, C. R., 19736, Metabolism of polycyclic aromadc hydrocarbons in cultured human leukocytes under genetic control, Humangenetik 20: 257–263.
Kellner, H. M., Carist, O. E., and Lotzsgh, K., 1973, Animal studies on the kinetics of benzidine and 3,3′-dichlorobenzidine, Arch. Toxikol. 31: 61–79.
Keysell, G. R., Booth, J., Grover, P. L., Hewer, A., and Sims, P., 1973, The formation of “K-region” epoxides as hepatic microsomal metabolite of 7-methylbenz(a)anthracene and 7,12- dimethylbenz(a)anthracene and their 7-hydroxymethyl derivatives, Biochem. Pharmacol. 22: 2853–2867.
King, C. M., and Olive, C. W., 1973, Comparative effects of age, strain and species on the activation of N-hydroxy-2-fluorenylacetamide (N-hydroxy-FAA) by soluble acyltransferases, Proc. Am. Assoc. Cancer Res. 14: 41.
King, C. M., Bednar, T. W., and Linsmaier-Bednar, E. M., 1973, Activation of the carcinogen N-hydroxy-2-fluorenylacetamide: Insensitivity to cyanide and sulfide of the peroxidase H2O2 induced formation of nucleic adducts, Chem.-Biol. Interact. 7: 185–188.
Kleihues, P., and Patzsghke, K., 1971, Verteilung von N-(14C) Methyl-N-nitroharnstoff in der Ratte nach systemischer Applikation, Z. Krebsforsch. 75: 193–200.
Kobayashi, A., and Matsumoto, H., 1965, Studies on methylazoxymethanol, the aglucone of cycasin. Arch. Biochem. Biophys. 110: 373–380.
Kouri, R. E., Ratrie, H., and Whitmore, C. E., 1973, Evidence of a genetic relationship between susceptibility to 3-methylcholanthrene-induced subcutaneous tumors and inducibility of aryl hydrocarbon hydroxylase, J. Natl. Cancer Inst. 51: 197–200.
Kriek, E., 1974, Carcinogenesis by aromatic amines, Biochimica et Biophysica Acta 355: 177–203.
Kreis, W., 1970, Metabolism of an antineoplastic methylhydrazine derivative in a P815 mouse neoplasm. Cancer Research 30: 82–89.
Krüger, F. W., 1971, Metabolism von Nitrosaminen in vivo, Z. Krebsforsch. 76: 145–154.
Krüger, F. W., 1973, New aspects in metabolism of carcinogenic nitrosamines, in: Topics in Chemical Carcinogenesis ( W. Nakahara, S. Takayama, T. Sugimura, and S. Odashima, eds.), pp. 213–235, University Park Press, Baltimore.
Krüger, F. W., and Bertram, B., 1973, Metabolism of nitrosamines in vivo, Z. Krebsforsch. 80: 189–196.
Kubinski, H., Strangstalien, M. A., Baird, W. M., and Boutwell, R. K., 1973, Interactions of phorbol esters with cellular membranes in vitro, Cancer Res. 33: 3103–3107.
Kunz, W., Schaude, G., and Thomas, C., 1969, Die Beeinflussung der Nitrosamincarcinogenese durch Phénobarbital und Halogenkohlenwasserstoffe, Z. Krebsforsch. 72: 291–304.
Lambelin, G., Mees, G., and Buu-Hoi, Ng. P., 1967, Chronic toxicity of 6-aminochrysene in the rat, Arzneimittel-Forschung 17: 117–1121.
Laqueur, G. L., 1970, Contribution of intestinal macroflora and microflora to carcinogenesis, in: Carcinoma of the Colon and Antecedent Epithelium, (W. J. Burdette, ed.), pp. 305–313, Thomas, Springfield, 111.
Legator, M.S., 1973, Procedure for conducting the host-mediated assay utilizing bacteria (Salmonella typhimurium), Agents Actions 3: 111–115.
Lijinsky, W., 1974, Reaction of drugs with nitrous acid as a source of carcinogenic nitrosamies. Cancer Res. 34: 255–258.
Lijinsky, W., Keefer, L., Loo, J., and Ross, A. E., 1973, Studies of alkylation of nucleic acids in rats by cyclic nitrosamines. Cancer Res. 33: 1634–1641.
Litwak, G., Morey, K. S., and Ketterer, B., 1972, Corticosteroid binding proteins of liver cytosol and interactions with carcinogens, in: Effects of Drugs on Cellular Control Mechanisms ( B. R. Rabin and R. B. Freedman, eds.), pp. 105–130, Macmillan, London.
Lotlikar, P. D., and Luha, L., 1971, Acetylation of the carcinogen N-hydroxy-2-acetylaminofluorene by acetyl coenzyme A to form a reactive ester, Mol. Pharmacol. 7: 381–388.
Lower, G. M., and Bryan, G. T., 1973, Enzymatic N-acetylation of carcinogenic aromatic amines by liver cytosol of species displaying different organ susceptibilities, Biochem. Pharmacol. 22: 1581–1588.
Magee, P. N., Hawks, A., Stewart, B. W., and Swann, P. F., 1973, Mechanisms of carcinogenesis by alkylnitrosamine and related compounds, in: Proceedings of the 5th International Congress of Pharmacology, Vol. 2, pp. 140–149, Karger, S., Basel and New York.
Magee, P. N., Montesano, R., and Preussmann, R., 1974, in: Chemical Carcinogens (C. Searle, ed.), American Chemical Society Monograph, Washington, D.C., in press.
Malejka-Giganti, D., Gutmann, H. R., and Rydell, R. E., 1973, Mammary carcinogenesis in the rat by topical application of fluorenylhydroxamic acids. Cancer Res. 33: 2489–2497.
Maltoni, C., and Lefemine, G., 1974, Le potenzialita dei saggi sperimentali nella predizionedei rischi» oncogeni ambientali. Un esempio: II cloruro di vinile, Lincei-Rend. Sci. Fis. Mat. Nat. 56: 1–11.
Matsumoto, H., Nagata, Y., Nishimura, E. T., Bristol, R., and Haber, M., 1972, β-GIucosidase modulation in preweanling rats and its association with tumor induction by cycasin, J. Natl. Cancer Inst. 49: 423–434.
Matsushima, T., Grantham, P. H., Weisburger, E. K., and Weisburger, J. H., 1972, Phenobarbital- mediated increase in ring- and N-hydroxylation of the carcinogen iV-2-fluorenylacetamide, and decrease in amounts bound to liver deoxyribonucleic acid, Biochem. Pharmacol. 21: 2043–2051.
Matsuyama, A., and Nagata, C., 1973, Detection of the unstable intermediate 4-nitrosoquinoline 1-oxide, in: Topics in Chemical Carcinogenesis ( W. Nakahara, S. Sakayama, T. Sagimura and S. Odashima, eds.), pp. 35–51, University Park Press, Baltimore.
Mattocks, A. R., and White, I. N. H., 1973, Toxic effects and pyrrolic metabolites in the liver of young rats given the pyrrolizidine alkaloid retrorsine, Chem.-Biol. Interact. 6: 297–306.
McCuen, R. W., Stöhrer, G., and Sirotnak, F. M., 1974, Mutagenicity of derivatives of the oncogenic purine-N-oxides, Cancer Res. 34: 378–384.
McDonald, J. J., Stöhrer, G., and Brown, G. B., 1973, Oncogenic purine N-oxide derivatives as substrates for sulfotransferase, Cancer Res. 33: 3319–3323.
McLean, A. E. M., 1970, The effect of protein deficiency and microsomal enzyme induction by DDT and phenobarbitone on the acute toxicity of chloroform and a pyrrolizidine alkaloid, retrorsine, Brit. J. Exp. Pathol. 51: 317–321.
McLean, A. E. M., and Magee, P. N., 1970, Increased renal carcinogenesis by dimethylnitrosamine in protein deficient rats, Brit. J. Exp. Pathol. 51: 587–590.
McLean, A. E. M., and Marshall, A., 1971, Reduced carcinogenic effect of aflatoxin in rats given phenobarbitone, Brit. J. Exp. Pathol. 52: 322–329.
McLean, E. K., McLean, A. E. M., and Sutton, P. M., 1969, Instant cirrhosis, Brit. J. Exp. Pathol. 50: 502–506.
Miller, E. C., and Miller, J. A., 1967, Low carcinogenicity of the K-region epoxides of 7-methylbenz(a)anthracene and benz(a)anthracene in the mouse and rat, Proc. Soc. Exp. Biol. Med. 124: 915–919.
Miller, E. C., and Miller, J. A., 1971, The mutagenicity of chemical carcinogens: Correlations, problems, and interpretations, in: Chemical Mutagens ( A. Hollaender, ed.), pp. 83–119, Plenum Press, New York.
Miller, E. C., and Miller, J. A., 1972, Approaches to the mechanisms and control of chemical carcinogenesis, in: Environment and Cancer, pp. 5–39, Williams and Wilkins, Baltimore.
Miller, E. C., Miller, J. A., and Enomoto, M., 1964, The comparative carcinogenicities of 2-acetylaminofluorene and its N-hydroxy metabolite in mice, hamsters, and guinea pigs, Cancer Res. 24: 2018–2031.
Miller, J. A., 1970, Carcinogenesis by chemicals: An overview. Cancer Res. 30: 559–576.
Miller, J. A., 1973, Naturally occurring substances that can induce tumors, in: Toxicants Occurring Naturally in Foods, pp. 509–548, National Academy of Sciences, Washington, D.C.
Miller, J. A., and Miller, E. C., 1971, Chemical carcinogenesis: Mechanisms and approaches to its control, J. Natl. Cancer Inst. 47:V–XIII.
Mirkin, B. L., 1970, Developmental pharmacology, Ann. Rev. Pharmacol. 10: 255–272.
Mirvish, S. S., 1968, The carcinogenic action and metabolism of urethan and N-hydroxyurethan, Advan. Cancer Res. 11: 1–42.
Mirvish, S. S., 1972, Kinetics of N-nitrosation reactions in relation to tumorigenesis experiments with nitrite plus amines or ureas, in: N-Nitroso Compounds: Analysis and Formation, pp. 104–108, International Agency for Research on Cancer, Lyon.
Mirvish, S. S., and Chu, C., 1973, Chemical determination of methylnitrosourea and ethylni- trosourea in stomach content of rats, after intubation of the alkylureas plus sodium nitrite, J. Natl. Cancer Inst. 50: 745–750.
Mirvish, S. S., and Sidransky, H., 1971, Labeling in vivo of rat liver proteins by tritium-labeled dimethylnitrosamine, Biochem. Pharmacol. 20: 3493–3499.
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Davis, D. C., Gillette, J. R., and Brodie, B. B., 1973, Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism, J. Pharmacol. Exp. Ther. 187: 185–194.
Montesano, R., and Magee, P. N., 1974, Comparative metabolism in vitro of nitrosamines in various animal species including man, in: Chemical Carcinogenesis Essays ( R. Montesano, L. Tomatis, and W. Davis, Eds.), pp. 39–56, International Agency for Research on Cancer, Lyon.
Montesano, R., Saint Vincent, L., and Tomatis, L., 1973, Malignant transformation in vitro of rat liver cells by dimethylnitrosamine and N-methyl-N′-nitro-N-nitrosoguanidine, Brit. J. Cancer 28: 215–220.
Moule, Y., and Frayssinet, C., 1972, Enzymic conversion of aflatoxin BI to a derivative inhibiting in vitro transcription, FEBS Letters 25: 52–56.
Nair, P. P., and Kayden, H. J., 1972, International conference on vitamin E and its role in cellular metabolism, Ann. N.Y. Acad. Sci. 203: 1–247.
Nakajima, T., and Iwahara, S., 1973, Mutagenicity of dimethylnitrosamine in the metabolic process by rat liver microsomes. Mutation Res. 18: 121–127.
Narisawa, T., Nakano, H., Hayakawa, M., Sato, T., and Sakuma, A., 1973, Tumors of the colon and rectum induced by N-methyl-N′-nitro-N-nitrosoguanidine, in: Topics in Chemical Carcinogenesis ( W. Nakahara, S. Takayama, T. Sugimura, and S. Adashima, eds.), p. 145, University Park Press, Baltimore.
Narisawa, T., Magadia, N. E., Weisburger, J. H., and Wynder, E. L., 1974, Promoting effect of bile acid on colon carcinogenesis after intrarectal instillation of N-methyl-N-nitro-N-nitroso-guanidine in rats, J. Natl. Cancer Inst. 53: 1093–1097.
Nebert, D. W., and Gelboin, H. V., 1968, Substrate-inducible microsomal aryl hydroxylase in mammalian cell culture, J. Biol. Chem. 243: 6242–6249.
Nebert, D. W., Bausserman, L. L., and Bates, R. R., 1970, Effect of 17β-estradiol and testosterone on aryl hydrocarbon hydroxylase activity in mouse tissues in vivo and in cell culture. Int. J. Cancer 6: 470–475.
Nebert, D. W., Considine, N., and Owens, S. S., 1973, Genetic expression of aryl hydrocarbon hydroxylase induction. VI. Control of other aromatic hydrocarbon-inducible mono-oxygenase activities at or near the same genetic locus. Arch. Biochem. Biophys. 157: 148–159.
Nemoto, N., and Takayama, S., 1973, Formation of N7-methylguanidine in nuclear DNA and cytoplasmic RNA in mice on continuous oral administration of dimethylnitrosamine-3H solution, Z. Krebsforsch. 80: 113–125.
Neunhoeffer, O., Wilhelm, G., and Lehmann, G., 1970, Eine enzymatische Umlagerung can- cerogener Nitrosamine, Z. Naturforsch. 25: 302–307.
Newberne, P. M., 1974, Section 3, Report of discussion group No. 2 Diets in: Carcinogenesis Testing of Chemicals (L. Golberg, ed.) pp. 17–20, CRC Press, Cleveland, Ohio.
Oesch, P., 1973, Mammalian epoxide hydrases: Inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds, Xenobiotica 3: 305–340.
Oesch, P., Jerina, D. M., Daly, J. W., and Rice, J. M., 1973, Induction, activation and inhibition of epoxide hydrase: An anomalous prevention of chlorobenzene-induced hepatotoxicity by an inhibitor of epoxide hydrase, Chem.-Biol. Interact. 6: 189–202.
O’Gara, R. W., and Adamson, R. H., 1972, Spontaneous and induced neoplasms in nonhuman primates, in: Pathology of Simian Primates, Part I, pp. 190–238, Karger, Basel.
Okada, M., and Suzuki, E., 1972, Metabolism of butyl(4-hydroxybutyl)-nitrosamine in rats, Gann 63: 391.
Olson, W. A., Habermann, R. T., Weisburger, E. K., Ward, J. M., and Weisburger, J. H., 1973, Induction of stomach cancer in rats and mice by halogenated aliphatic fumigants, J. Natl. Cancer Inst. 51: 1993–1995.
Paine, A. J., and McLean, A. E. M., 1973, The effect of dietary protein and fat on the activity of aryl hydrocarbon hydroxylase in rat liver, kidney and lung, Biochem. Pharmacol. 22: 2875–2880.
Pantuck, E. J., Hsaio, K. C., Maggis, A., Nakamura, K., Kuntzman, R., and Conney, A. H., 1974, Effect of cigarette smoking on phenacetin metabolism, Clin. Pharmacol. Ther. 15: 9–17.
Patterson, D. S. P., 1973, Metabolism as a factor in determining the toxic action of the aflatoxins in different animal species. Food Cosmet. Toxicol. 11: 287–294.
Patterson, D. S. P., and Roberts, B. A., 1972, Steroid sex hormones as inhibitors of aflatoxin metabolism in liver homogenates, Experientia, 929–930.
Pelkonen, O., Kaltiala, E. O., Larmi, T. K. I., and Karki, N. T., 1973, Comparison of activities of drug metabolizing enzymes in human fetal and adult livers, Clin. Pharmacol. Ther. 14: 840–846.
Peraino, C., Fry, R. J., and Staffeldt, E., 1971, Reduction and enhancement by phénobarbital of hepatocarcinogenesis induced in the rat by 2-acetylaminofluorene, Cancer Res. 31: 1506–1512.
Poirier, L. A., and Weisburger, J. H., 1973, Enzymic reduction of carcinogenic aromatic nitro compounds by rat and mouse liver fractions, Biochem. Pharmacol. 23: 661–669.
Popper, H., Czygan, P., Greim, H., Schaffner, F., and Gano, A. J., 1973, Mutagenicity of primary and secondary carcinogens altered by normal and induced hepatic microsomes, Proc. Soc. Exp. Biol. Med. 142: 727–729.
Pound, A. W., Lawson, T. A., and Horn, L., 1973, Increased carcinogenic action of dimethylni- trosamine after prior administration of carbon tetrachloride, Brit. J. Cancer 27: 451–459.
Pozharisski, K. M., Kapustin, J. M., Likhachev, A. Y., and Shaposhnikov, Y. D., 1974, The dynamics of the rat tissue methylation in symmetric dimethylhydrazine-3H administration, Voprosy Onkol. 20(l):69–76.
Preussmann, R., 1974, Formation of carcinogens from precursors occurring in the environment: New aspects of nitrosamine-induced tumorigenesis, in: Special Topics in Carcinogenesis ( E. Grundmann, ed.) Vol. 44, pp. 9–15, Springer-Verlag, New York, Heidelberg, Berlin.
Preussman, R., Hengy, H. and Druckrey, H., 1965, Studies on the detection of alkylating agents. I. Spectrophotometric determination of diazoalkanes with 4-(4-nitrobenzyl)pyridinium perchlorate, Chem. Ann. 684: 57.
Prough, R. A., Wittkop, J. A., and Reed, D. J., 1970, Further evidence on the nature of microsomal metabolism of procarbazine and related alkylhydrazones. Arch. Biochem. Biophys. 140: 450–458.
Purchase, I. F. H., Steyn, M., and Gilfillan, T. C., 1973, Metabolism and acute toxicity to aflatoxin B1 in rats, Chem.-Biol. Interact. 7: 283–287.
Radomski, J. L., Conzelman, G. M., Jr., Rey, A. A., and Brill, E., 1973a, The N-oxidation of certain aromatic amines, acetamides and nitro compounds by monkeys and dogs, J. Natl. Cancer Inst. 50: 989–995.
Radomski, J. L., Rey, A. A., and Brill, E., 1973b, Evidence for a glucuronic acid conjugate of iV-hydroxy-4-aminobiphenyl in the urine of dogs given 4-aminobiphenyl, Cancer Res. 33: 1284–1289.
Raineri, R., and Weisburger, J. H., 1974, Role of the reduction of dietary nitrate to nitrite in the etiology of gastric cancer, Proc. Am. Assoc. Cancer Res. 15: 39.
Rao, K. V. N., and Vesselinovitch, S. D., 1973, Age- and sex-associated diethylnitrosamine dealkylation activity of the mouse liver and hepatocarcinogenesis. Cancer Res. 33: 1625–1627.
Recknagel, R. O., 1967, Carbon tetrachloride hepatotoxicity, Pharmacol. Rev. 19: 145–208.
Reddy, B. S., Pleasants, J. R., and Wostmann, B. S., 1973, Metabolic enzymes in liver and kidney of the germfree rat, Biochim. Biophys. Acta 320: 1–8.
Reddy, B. S., Weisburger, J. H., and Wynder, E. L., 1974a, Effects of dietary fat level and dimethylhydrazine on fecal acid and neutral sterol excretion and colon carcinogenesis in rats, J. Natl. Cancer Inst. 52: 507–511.
Reddy, B. S., Weisburger, J. H., Narisawa, T., and Wynder, E. L., 19746, Colon carcinogenesis in germfree rats with 1,2-dimethylhydrazine and N-methyl-N′-nitro-N-nitrosoguanidine, Cancer Res., 34: 2368–2372.
Reddy, J. K., Svoboda, D. J., and Rao, M. S., 1974, Susceptibility of an inbred strain of guinea pigs to the induction of pancreatic adenocarcinoma by N-methyl-N-nitrosourea, J. Natl. Cancer Inst. 52: 991–993.
Reuber, M. D., and Glover, E. L., 1970, Cirrhosis and carcinoma of the liver in male rats given subcutaneous carbon tetrachloride, J. Natl. Cancer Inst. 44: 419–427.
Rice, J. M., 1973, An overview of transplacental chemical carcinogenesis. Teratology 8: 113–126.
Rivlin, R. S., 1973, Riboflavin and cancer: A review. Cancer Res. 33: 1977–1986.
Rogers, A. E., Sanchez, O., Feinsod, F. M., and Newberne, P. M., 1974, Dietary enhancement of nitrosamine carcinogenesis. Cancer Res. 34: 96–99.
Rumack, B. H., Holtzman, J., and Chase, H. P., 1973, Hepatic drug metabolism and protein malnutrition, J. Pharmacol. Exp. Ther. 186: 441–446.
Sander, J., 1971, Untersuchungen über die Entstehung cancerogener Nitrosoverbindungen im Magen von Versuchstieren und ihre Bedeutung für den Menschen, Arzneimittel-Forschung 21:1572–1580, 1707–1713, 2034–2039.
Sander, J., 1973, The formation of N-nitroso compounds in the stomach of animal and man and in the diet, in: Transplacental Carcinogensis, International Agency for Research on Cancer, Lyon.
Sander, J., Schweinsberg, F., Ladenstein, M., Benzing, H., and Wahl, S. A., 1973, Messung der renalen Nitrosaminausscheidung am Hund zum Nachweis einer Nitrosaminbildung in vivo, Hoppe-Seylers Z. Physiol. Chem. 354: 384–390.
Sawicki, E., and Sawicki, C. R., 1969, Analysis of alkylating agents: Applications to air pollution, Ann. N.Y. Acad. Sci. 163: 895–920.
Scheline, R. R., 1973, Metabolism of foreign compounds by gastrointestinal microorganisms, Pharmacol. Rev. 24: 451–523.
Schmähl, D., 1970, Entstehung, Wachstum und Chemotherapie maligner Tumoren, Cantor, Aulen¬dorf.
Schmall, B., Cheng, C. J., Fujimura, S., Gerstein, N., Grunbercíer, D., and Weinstein, L B., 1973, Modification of proteins by l-(2-chloroethyl)-3-cyclohexyI-l-nitrosourea (NSC 79037) in vitro, Cancer Res. 33: 1921–1924.
Schoental, R., 1970, Hepatotoxic activity of retrorsine, senkirkine and hydroxysenkirkine in newborn rats, and the role of epoxides in carcinogenesis by pyrrolizidine alkaloids and aflatoxins. Nature (Lond.) 227: 401–402.
Schoental, R., 1973, The mechanisms of action of the carcinogenic nitroso and related compounds, Brit. J. Cancer 28: 436–439.
Schwartz, A. G., 1974, Protective effect of benzoflavone and estrogen against 7,12- dimethylbenz(a)anthracene- and aflatoxin-induced cytotoxicity in cultured liver cells. Cancer Res, 34: 10–15.
Selikoff, L J., and Hammond, E. C.. 1974, Working group: Toxicity of vinyl chloride—Polyvinyl chloride, New York Academy of Sciences meeting. Ann. N.Y. Acad. Sci., in press.
Selkirk, J. K., Huberman, E., and Heidelberger, C., 1971, An epoxide is an intermediate in the microsomal metabolism of the chemical carcinogen, dibenz(a,h)anthracene, Biochem. Biophys. Res. Commun. 43: 1010–1016.
Selkirk, J. K., Grog, R. G., and Gelboin, H. V., 1974, Benzo(a)pyrene metabolites: Efficient and rapid separation by high-pressure liquid chromatography. Science 184: 169–171.
Sivak, A., and Van Duuren, B. L., 1971, Cellular interactions of phorbol myristate acetate in tumor promotion, Chem.-Biol. Interact. 3: 401–411.
Skibba, J. L., Beal, D. D., Ramirez, G., and Bryan, G. T., 1970a, N-Demethylation of the antineoplastic agent 4(5)-(3,3-dimethyl-l-triazeno)imidazole-5(4)-carboxamide by rats and man. Cancer Res. 30: 147–150.
Skibba, J. L., Ramirez, G., Beal, D. D., and Bryan, G. T., 1970b, Metabolism of 4(5)-(3,3-dimethyl-l- triazeno)imidazole-5(4)-carboxamide to 4(5)-aminoimidazole-5(4)-carboxamide in man, Biochem. Pharmacol. 19: 2043–2051.
Smith, R. G., and Pollard, D. R., 1969, Excretion of S-adenosylethionine in the urine of rats fed a diet containing ethionine, Biochim. Biophys. Acta 184: 397–403.
Smith, R. L., 1973, The Excretory Function of Bile, Chapman and Hall, London.
Smuckler, E. A., 1972, The pathology of halogenated hydrocarbons and halothane: A brief review and speculation, in: Cellular Biology and Toxicity of Anaesthetics ( B. R. Fink, ed.), pp. 221–237, Williams and Wilkins Co., Baltimore.
So, B. T., and Wynder, E. L., 1972, Induction of hamster tumors of the urinary bladder by 3,2′-dimethyl-4-aminobiophenyl, J. Natl. Cancer Inst. 48: 1733–1738.
So, B. T., Magadia, N. E., and Wynder, E. L., 1973, Induction of carcinomas of the colon and rectum in rats by intrarectal instillation of N-methyl-N′-nitro-N-nitrosoguanidine, J. Natl. Cancer Inst. 50: 927–932.
Spjut, H. J., 1972, Newer concepts of cancer of the colon and rectum: Similarities between human and experimentally induced tumors of the large intestine, Dis. Colon Rectum 15: 94–99.
Stöhrer, G., Salemnick, G., and Brown, G. B., 1973, A chemical adduct of tryptophan and the oncogen 3-acetoxyxanthine, Biochemistry 12: 5084–5086.
Stoltz, D. R., Poirier, L. A., Irving, C. C., Stich, H. F., Weisburger, J. H., and Grice, H. C., 1974, Evaluation of short term tests for carcinogenicity, Toxicol. Appl. Pharmacol. 29: 157–180.
Stoming, T., Knapp, D., and Bresnick, E., 1973, Gas chromatographic separation of K-region epoxide and of the cis- and-trans-11,12-diol derivatives of 3-methylcholanthrene, Life Sci. 12: 425–429.
Sugimura, T., Okabe, T., and Nagao, M., 1966, Metabolism of 4-nitroquinoline 1-oxide, a carcinogen. III. Enzyme catalyzing the conversion of 4-nitroquinoline 1-oxide to 4-hydroxyaminoquinoline 1-oxide in rat liver and heptomas. Cancer Res. 27: 1717–1721.
Sugimura, T., Kawachi, T., Kogura, K., Nagao, M., Tanaka, N., Fujimura, S., Takayama, S., Shimosato, Y., Noguchi, M., Kuwabara, N., and Yamada, T., 1973, Induction of stomach cancer by N-methyl-N′-nitro-N′nitrosoguanidine: Experiments in dogs as clinical models and the metabolism of this carcinogen, in: Topics in Chemical Carcinogenesis ( W. Nakahara, S. Takayama, T. Sugimura, and S. Odashima, eds.), pp. 105–119, University Park Press, Baltimore.
Sullman, S. F., Armstrong, S. J., Zuckerman, A. J., and Rees, K. R., 1970, Further studies on the toxicity of the aflatoxins on human cell cultures, Brit. J. Exp. Pathol. 51: 314–316.
Sunderman, F. W., Jr., 1971, Metal carcinogenesis in experimental animals. Food Cosmet. Toxicol. 9: 105–120.
Swann, P. F., and McLean, A. E. M., 1971, The effect of a protein-free high-carbohydrate diet on the metabolism of dimethylnitrosamine in the rat, Biochem. J. 124: 283–288.
Swenson, D. H., Miller, J. A., and Miller, E. C., 1973, 2,3-Dihydro-2,3-dihydroxy-afiatoxin B1: An acid hydrolysis product of an RNA-aflatoxin Bi adduct formed by hamster and rat liver microsomes in vitro, Biochem. Biophys. Res. Commun. 53: 1260–1267.
Swenson, H., Miller, J. A., and Miller, E. C., 1974, AflatoxinB1-2,3-dichloride: A toxic and reactive derivative of aflatoxin B1, Proc. Am. Assoc. Cancer Res. 15: 43.
Tanaka, A., and Sano, T., 1971, Metabolism of N-methyl-iV-nitro-N-nitrosoguanidine in rats, Experientia 27: 1007–1008.
Terayama, H., 1967, Aminoazo carcinogenesis—Methods and biochemical problems, Meth. Cancer Res. 1: 399–449.
Thorgeirsson, S. S., Jollow, D. J., Sasame, H. A., Green, I., and Mitchell, J. R., 1973, The role of cytochrome P-450 in N-hydroxylation of 2-acetylaminofluorene, Mol. Pharmacol. 9: 398–404.
Tomatis, L., Mohr, U., and Davis, W., 1973a, Transplacental Carcinogenesis, International Agency for Research on Cancer, Lyon.
Tomatis, L., Partensky, C., and Montesano, R., 1973b, The predictive value of mouse liver tumor induction in carcinogenicity testing—A literature survey, Int. J. Cancer 12: 1–20.
Toth, B., 1968, A critical review of experiments in chemical carcinogenesis using newborn animals, Cancer Res. 28: 727–738.
Toth, B., and Shimizu, H., 1973, Methylhydrazone tumorigenesis in Syrian golden hamsters and the morphology of malignant histiocytomas, Cancer Res. 33: 2744–2753.
Ts’o, P. O. P., and DiPaolo, J. A., eds., 1974, Chemical Carcinogenesis, Marcel Dekker, Inc., New York.
Uehleke, H., 1973, The role of cytochrome P-450 in the N-oxidation of individual amines. Drug Metab. Disposition 1: 299–313.
Uehleke, H., Hellmer, K. H., and Tabarelli, S., 1973, Binding of 14C-carbon tetrachloride to microsomal proteins in vitro and formation of CHCI3 by reduced liver microsomes, Xenobiotica 3: 1–11.
Uraguchi, K., Ueno, I., Ueno, Y., and Komai, Y., 1972, Absorption, distribution and excretion of luteoskyrin with special reference to the selective action on the liver, Toxicol. Appl. Pharmacol. 21: 335–347.
Van Duuren, B. L., Katz, C., and Goldschmidt, B. M., 1973, Cocarcinogenic agents in tobacco carcinogenesis, J. Natl. Cancer Inst. 51: 703–705.
Venkatesan, N., Argus, M. F., and Arcos, J. C., 1970, Mechanism of 3-methylcholanthrene-induced inhibition of dimethylnitrosamine demethylase in rat liver, Cancer Res. 30: 2556–2562.
Vesselinovitch, S. D., Mihailovich, N., Wogan, G. N., Lombard, L. S., and Rao, V. N., 1972, Aflatoxin Bi, a hepatocarcinogen in the infant mouse. Cancer Res. 32: 2289–2291.
Visek, W. J., 1972, Effects of urea hydrolysis on cell lifespan and metabolism. Fed. Proc. 31: 1178–1193.
Waterfall, J. F., and Sims, P., 1973, The metabolism of dibenzo(a,h)pyrene and dibenzo(a,i)pyrene and related compounds by liver preparations and their enzyme induced binding to cellular macromolecules, Biochem. Pharmacol. 22: 2469–2483.
Wattenberg, L. W., 1972, Dietary modification of intestinal and pulmonary aryl hydrocarbon hydroxylase activity, Toxicol. Appl. Pharmacol. 23: 741–748.
Wattenberg, L. W., 1973, Inhibition of chemical carcinogen-induced pulmonary neoplasia by butylated hydroxyanisole, J. Natl. Cancer Inst. 50: 1541–1544.
Weisburger, J. H., 1973a, Chemical carcinogenesis, in: Cancer Medicine ( J. F. Holland and E. Frei, eds.), pp. 45–91, Lea and Febiger, Philadelphia.
Weisburger, J. H., 1973b, Chemical carcinogenesis in the gastrointestinal tract, in: Seventh National Cancer Proceedings, pp. 465–473, American Cancer Society, New York.
Weisburger, J. H., 1974, Assessment of human exposure and response to N-nitroso compounds: A new view on the etiology of digestive tract cancers, Toxicol. Appl. Pharmacol., in press.
Weisburger, J. H., and Rall, D. P., 1972, Do animal models predict carcinogenic hazards for man? in: Environment and Cancer, pp. 437–452, Williams and Wilkins, Baltimore.
Weisburger, J. H., and Weisburger, E. K., 1973, Biochemical formation and pharmacological, toxicological, and pathological properties of hydroxylamines and hydroxamic acids, Pharmacol. Rev. 25: 1–66.
Weisburger, J. H., Hadidian, Z., Frederickson, T. N., and Weisburger, E. K., 1967, Host properties determine target, bladder or liver in chemical carcinogenesis, in: Bladder Cancer: A Symposium ( W. B. Deichmann and K. F. Lampe, eds.), pp. 45–57, Aesculapius, Birmingham, Ala.
Weisburger, J. H., Yamamoto, R. S., Glass, R. M., and Frankel, H. H., 1969, Prevention by arginine glutamate of the carcinogenicity of acetamide in rats, Toxicol. Appl. Pharmacol. 14: 163–175.
Weisburger, J. H., Yamamoto, R. S., Williams, G. M., Grantham, P. H., Matsushima, T., and Weisburger, E. K., 1972, On the sulfate ester of N-hydroxy-N-2-fluorenylacetamide as a key ultimate hepatocarcinogen in the rat. Cancer Res. 32: 491–500.
Weisburger, J. H., Griswold, D. P., Jr., Prejean, J. D., Casey, A. E., Wood, H. B., Jr., and Weisburger, E. K., 1974, The carcinogenic properties of some of the principal drugs used in clinical cancer chemotherapy, Rec. Results Cancer Res., in press.
Wiebel, F. J., Leutz, J. C., and Gelboin, H. V., 1973, Aryl hydrocarbon (benzo(a)pyrene) hydroxylase: Ihducible in extrahepatic tissues of mouse strains, not inducible in liver. Arch. Biochem. Biophys. 154: 292–294.
Williams, D. J., and Rabin, B. R., 1971, Distribution by carcinogens of the hormone dependent association of membranes with polysomes. Nature 232: 102–105.
Williams, G. M., Elliot, J. M., and Weisburger, J. H., 1973, Carcinoma after malignant conversion in vitro of epithelial like cells from rat liver following exposure to chemical carcinogens. Cancer Res. 33: 606–612.
Williams, J. R., Jr., Grantham, P. H., Marsh, H. H., III, Weisburger, J. H., and Weisburger, E. K., 1970, The participation of liver fractions and of intestinal bacteria in the metabolism of N-hydroxy- N-2-fluorenylacetamide in the rat, Biochem. Pharmacol. 19: 173–188.
Williams, R. T., 1972, Toxicological implications of biotransformation by intestinal microflora, Toxicol. Appl. Pharmacol. 23: 769–781.
Wogan, G. N., 1973, Aflatoxin carcinogenesis, in: Methods in Cancer Research, Vol. VII, pp. 309–344, Academic Press, New York.
Wynder, E. L., 1974, Working groups in cancer etiology. Cancer Res. 34: 1516–1518.
Wynder, E. L., and Hoffmann, D., 1967, Tobacco and Tobacco Smoke, Academic Press, New York.
Wynder, E. L., and Mabuchi, K., 1972, Etiological and preventive aspects of human cancer, Preventive Med. 1: 300–334.
Wynder, E. L., and Reddy, B. S., 1973, Studies in large-bowel cancer: Human leads to experimental application, J. Natl. Cancer Inst. 50: 1099–1106.
Yahagi, T., Nagao, M., Hara, K., Matsushima, T., Sugimura, T., and Bryan, G. T., 1974, Relationship between the carcinogenic and mutagenic or DNA-modifying effects of nitrofuran derivatives, including AF-2, a food additive widely used in Japan, Cancer Res. 34: 2266–2273.
Yamamoto, R. S., Weisburger, J. H., and Weisburger, E. K., 1971, Controlling factors in urethan carcinogenesis in mice: Effect of enzyme inducers and metabolic inhibitors, Cancer Res. 31: 483–486.
Yang, C. S., 1973, Alterations of the aryl hydrocarbon hydroxylase system during riboflavin depletion and repletion. Arch. Biochem. Biophys. 160: 623–630.
Yeh, Y.-Y., and Johnson, R. M., 1973, Vitamin E deficiency in the rat. IV. Alteration in mitochondrial membrane and its relation to respiratory decline. Arch. Biochem. Biophys. 159: 821–831.
Yoshida, O., and Miyakawa, M., 1973, Etiology of bladder cancer: “Metabolic” aspects, in: Analytic and Experimental Epidemiology of Cancer ( W. Nakahara, T. Hirayama, K. Nishioka, and H. Sugano, eds.), pp. 31–39, University Park Press, Baltimore.
Zachariah, P. K., and Juchau, M. R., 1974, The role of gut flora in the reduction of aromatic nitro-groups. Drug Metab. Disposition 2: 74–78.
Zampaglione, N., Jollow, D. J., Mitchell, J. R., Stripp, B., Hamrick, M., and Gillette, J. R., 1973, Role of detoxifying enzymes in bromobenzene-induced liver necrosis, J. Pharmacol. Exp. Ther. 187: 218–227.
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Weisburger, J.H., Williams, G.M. (1975). Metabolism of Chemical Carcinogens. In: Becker, F.F. (eds) Cancer. A Comprehensive Treatise. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4449-0_7
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