The metabolism of xenobiotics to reactive electrophiles in chemical carcinogenesis and mutagenesis: A collaboration with Elizabeth Cavert Miller and our associates

Drug Metabolism Reviews

Volumn 30, Issue 4, 1998, Pages 645-674

  Miller, James A ^a  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANILINE DERIVATIVE; AZO DYE; CARCINOGEN; DRUG METABOLITE; FLUORINE DERIVATIVE; MICROSOME ENZYME; MUTAGENIC AGENT; NUCLEIC ACID; PROTEIN; XENOBIOTIC AGENT;

CHEMICAL CARCINOGENESIS; CHEMICAL MUTAGENESIS; CHEMICAL STRUCTURE; COVALENT BOND; DNA BINDING; ENZYME INDUCTION; HUMAN; LIVER MICROSOME; NONHUMAN; PROTEIN BINDING; REVIEW; XENOBIOTIC METABOLISM;

EID: 0031726163     PISSN: 03602532     EISSN: None     Source Type: Journal    
DOI: 10.3109/03602539808996326     Document Type: Review

References (111)

1. T. Sasaki and T. Yoshida, Experimentelle Erzeugung des Lebercarcinomas durch Futterung mit o-Amidoazotoluol, Virchow's Arch. Pathol. Anat. Physiol., 295, 175-200 (1935).
2. R. Kinosita, Studies on the cancerogenic chemical substances, Trans. Jpn. Pathol. Soc., 27, 665-727 (1937).
3. E. S. Stevenson, K. Dobriner, and C. P. Rhoads, The metabolism of dimethylaminoazobenzene (butter yellow) in rats, Cancer Res., 2, 160-167 (1942).
4. J. A. Miller and C. A. Baumann, The determination of p-dimethylaminoazobenzene, p-monomethylaminoazobenzene, and p-aminoazobenzene in tissue, Cancer Res., 5, 157-161 (1945).
5. J. A. Miller, E. C. Miller, and C. A. Baumann, On the methylation and demethylation of certain carcinogenic azo dyes in the rat, Cancer Res., 5, 162-168 (1945).
6. J. A. Miller and C. A. Baumann, The carcinogenicity of certain azo dyes related to p-dimethylaminoazobenzene, Cancer Res., 5, 227-234 (1945).
7. J. A. Miller and E. C. Miller, The carcinogenic aminoazo dyes, Adv. Cancer Res., 7, 340-396 (1953).
8. E. C. Miller and J. A. Miller, The presence and significance of bound aminoazo dyes in the livers of rats fed p-dimethylaminoazobenzene, Cancer Res., 7, 468-480 (1947).
9. E. C. Miller, J. A. Miller, R. W. Sapp, and G. M. Weber, Studies on protein-bound aminoazo dyes formed in vivo from 4-dimethylaminoazobenzene and its C-monomethyl derivatives, Cancer Res., 9, 336-343 (1949).
10. E. C. Miller and J. A. Miller, In vivo combinations between carcinogens and tissue constituents and their possible role in carcinogenesis, Cancer Res., 12, 547-556 (1952).
11. S. Sorof, P. P. Cohen, E. C. Miller, and J. A. Miller, Studies on the soluble proteins from livers of rats fed aminoazo dyes, Cancer Res., 11, 383-387 (1951).
12. S. Sorof and P. P. Cohen, Electrophoretic and ultracentrifugal studies on the soluble proteins of various tumors and of livers from rats fed 4-dimethylaminoazobenzene, Cancer Res., 11, 376-383 (1951).
13. E. C. Miller, Studies on the formation of protein-bound derivatives of 3,4-benzpyrene in the epidermal fraction of mouse skin, Cancer Res., 11, 100-108 (1951).
14. M. Levine and H. Tarver, Studies of ethionine. III. Incorporation of ethionine into rat proteins, J. Biol. Chem., 192, 835-850 (1951).
15. 14 in skin, Cancer Res., 13, 250-254 (1953).
16. 14, Arch. Biochem. Biophys., 43, 474-484 (1953).
17. 14, Proc. Am. Assoc. Cancer Res., 4, 41 (1963).
18. J. -K. Lin, J. A. Miller, and E. C. Miller, Structures of hepatic nucleic acid-bound dyes in rats given the carcinogen N-methyl-4-aminoazobenzene, Cancer Res., 35, 844-850 (1975).
19. J. D. Watson and F. H. C. Crick, Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid, Nature (London), 171, 737-738 (1953).
20. 3 in nucleic acid fractions of animal tissues, Arch. Biochem. Biophys., 72, 465-475 (1957).
21. E. C. Miller and J. A. Miller, Mechanisms of chemical carcinogenesis. Nature of proximate carcinogens and interactions with macromolecules, Pharmacol. Rev., 18, 805-838 (1966).
22. E. C. Miller and J. A. Miller, Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules, Cancer, 47, 2327-2345 (1981).
23. V. R. Potter and C. A. Elvehjem, A modified method for the study of tissue oxidations, J. Biol. Chem., 114, 495-503 (1936).
24. C. J. Kensler, J. W. Magill, and K. Sugiura, The metabolism of N,N-dimethyl-p-aminoazobenzene, Cancer Res., 7, 95-98 (1947).
25. G. C. Mueller and J. A. Miller, The metabolism of 4-dimethylaminoazobenzene by rat liver homogenates, J. Biol. Chem., 176, 535-544 (1948).
26. W. F. Trager, Oxidative functionalization reactions, Drugs Pharm. Sci., 10(Part A), 177-210 (1980).
27. G. C. Mueller and J. A. Miller, The reductive cleavage of 4-dimethylaminoazobenzene by rat liver: The intracellular distribution of the enzyme system and its requirement for triphosphopyridine nucleotide, J. Biol. Chem., 180, 1125-1136 (1949).
28. G. C. Mueller and J. A. Miller, The reductive cleavage of 4-dimethylaminoazobenzene by rat liver: Reactivation of carbon dioxide-treated homogenates by riboflavin-adenine dinucleotide, J. Biol. Chem., 185, 145-154 (1950).
29. G. C. Mueller and J. A. Miller, The metabolism of methylated aminoazo dyes. II. Oxidative demethylation by rat liver homogenates, J. Biol. Chem., 202, 579-587 (1953).
30. B. N. La Du, L. Gaudette, N. Trousof, and B. B. Brodie, Enzymatic dealkylation of aminopyrine (Pyramidon) and other alkylamines, J. Biol. Chem., 214, 741-752 (1955).
31. J. Axelrod, The enzymatic deamination of amphetamine (Benzedrine), J. Biol. Chem., 214, 753-763 (1955).
32. B. B. Brodie, J. R. Gillette, and B. N. La Du, Enzymatic metabolism of drugs and other foreign compounds, Annu. Rev. Biochem., 27, 427-454 (1958).
33. R. R. Brown, J. A. Miller, and E. C. Miller, The metabolism of methylated dyes. IV. Dietary factors enhancing demethylation in vitro, J. Biol. Chem., 209, 211-222 (1954).
34. E. C. Miller, J. A. Miller, and A. H. Conney, On the mechanism of methylcholanthrene inhibition of carcinogenesis by 3′-methyl-4-dimethylaminoazobenzene, Proc. Am. Assoc. Cancer Res., 1(2), 32 (1954).
35. A. H. Conney, E. C. Miller, and J. A. Miller, Induction of enzyme synthesis in the rat liver by 3-methylcholanthrene, Proc. Am. Assoc. Cancer Res., 2, 101 (1956).
36. A. H. Conney, E. C. Miller, and J. A. Miller, The metabolism of methylated dyes. V. Evidence for the induction of enzyme synthesis in the rat by 3-methylcholanthrene, Cancer Res., 16, 450-459 (1956).
37. A. H. Conney, E. C. Miller, and J. A. Miller, Substrate-induced synthesis and other properties of benzpyrene hydroxylase in rat liver, J. Biol. Chem., 228, 753-766 (1957).
38. A. H. Conney, and A. E. Gilman, Puromycin inhibition of enzyme induction by 3-methylcholanthrene and phenobarbital, J. Biol. Chem., 238, 3682-3685 (1963).
39. H. V. Gelboin, and N. R. Blackburn, The stimulatory effect of 3-methylcholanthrene on microsomal amino acid incorporation and benzpyrene hydroxylase activity and its inhibition by actinomycin D, Biochim. Biophys. Acta, 72, 657-660 (1963).
40. H. L. Richardson, A. R. Stier, and E. Borsos-Nachtnebel, Liver tumor inhibition and adrenal histologic responses in rats to which 3′-methyl-4-dimethylaminoazobenzene and 20-methylcholanthrene were simultaneously administered, Cancer Res., 12, 356-361 (1952).
41. E. C. Miller, J. A. Miller, R. R. Brown, and J. S. MacDonald, On the protective effect of certain polycyclic aromatic hydrocarbons against carcinogenesis by aminoazo dyes and 2-acetylaminofluorene, Cancer Res., 18, 469-477 (1958).
42. A. H. Conney, Pharmacological implications of microsomal enzyme induction, Pharmacol. Rev., 19, 317-366 (1967).
43. H. S. Mason, Mechanisms of oxygen metabolism, Science, 125, 1185-1188 (1957).
44. H. S. Posner, C. Mitoma, S. Rothberg, and S. Udenfriend, Enzymic hydroxylation of aromatic compounds. III. Studies on the mechanism of microsomal hydroxylation, Arch. Biochem. Biophys., 94, 280-290 (1961).
45. 21 hydroxylation of steroids by adrenocortical microsomes, J. Biol. Chem., 238, 1320-1323 (1963).
46. D. Y. Cooper, S. Levin, S. Harasimhulu, O. Rosenthal, and R. W. Estabrook, Photochemical action spectrum of the terminal oxidase of mixed-function oxidase systems, Science, 147, 400-402 (1965).
47. M. J. Coon and A. V. Persson, Microsomal cytochrome P-450: A central catalyst in detoxication reactions, in Enzymatic Basis of Detoxication (W. B. Jakoby, ed.), Academic Press, New York, 1980, Vol. 1, pp. 117-134.
48. A. Y. H. Lu and S. H. West, Multiplicity of mammalian microsomal cytochromes P-450, Pharmacol. Rev., 31, 277-295 (1980).
49. P. G. Wislocki, G. T. Miwa, and A. Y. H. Lu, Reactions catalyzed by the cytochrome P-450 system, in Enzymatic Basis of Detoxication (W. B. Jakoby, ed.), Academic Press, New York, 1980, Vol. 1, pp. 135-182.
50. E. K. Weisburger and J. H. Weisburger, Chemistry, carcinogenicity and metabolism of 2-fluorenamine and related compounds, Adv. Cancer Res., 5, 331-431 (1956).
51. 2-fluorenylacetamide, J. Natl. Cancer Inst., 17, 345-361 (1950).
52. J. W. Cramer, J. A. Miller, and E. C. Miller, N-hydroxylation: A new metabolic reaction observed in the rat with the carcinogen 2-acetylaminofluorene, J. Biol. Chem., 235, 885-888 (1960).
53. E. C. Miller, J. A. Miller, and H. A. Hartmann, N-Hydroxy-2-acetylaminofluorene, a metabolite with increased carcinogenic activity in the rat, Cancer Res., 21, 815-824 (1961).
54. E. C. Miller, J. A. Miller, and M. Enomoto, The comparative carcinogenicities of 2-acetylaminofluorene and its N-hydroxy metabolite in mice, hamsters, and guinea pigs, Cancer Res., 24, 2018-2032 (1964).
55. F. A. Beland and F. F. Kadlubar, Metabolic activation and DNA adducts of aromatic amines and nitroaromatic hydrocarbons, in Chemical Carcinogenesis and Mutagenesis I (C. S. Cooper and P. L. Grover, eds.), Springer-Verlag, Berlin, 1990.
56. L. A. Poirier, J. A. Miller, E. C. Miller, and K. Sato, N-Benzoyloxy-N-methyl-4-aminobenzene: Its carcinogenic activity in the rat and its reactions with proteins and nucleic acids and their constituents in vitro, Cancer Res., 27, 1600-1613 (1967).
57. J. D. Scribner, J. A. Miller, and E. C. Miller, 3-Methylmercapto-N-methyl-4-aminoazobenzene: An alkaline-degradation product of a labile protein-bound dye in the livers of rats fed N,N-dimethyl-4-aminoazobenzene, Biochem. Biophys. Res. Commun., 20, 560-565 (1965).
58. P. D. Lotlikar, J. D. Scribner, J. A. Miller, and E. C. Miller, Reaction of esters of aromatic N-hydroxy amines and amides with methionine in vitro: A model for in vivo binding of amine carcinogens to protein, Life Sci., 5, 1263-1289 (1966).
59. E. C. Miller, U. Juhl, and J. A. Miller, Nucleic acid guanine: Reaction with the carcinogen N-acetoxy-2-acetylaminofluorene, Science, 153, 1125-1127 (1966).
60. E. Kriek, J. A. Miller, U. Juhl, and E. C. Miller, 8-(N-Fluorenylacetamido)-guanosine, an arylamidation reaction product of guanosine and the carcinogen N-acetoxy-N-fluorenylacetamide in neutral solution, Biochemistry, 6, 177-182 (1967).
61. J. R. DeBaun, J. Y. Rowley, E. C. Miller, and J. A. Miller, Sulfotransferase activation of N-hydroxy-2-acetylaminofluorene in rodent livers susceptible and resistant to this carcinogen, Proc. Soc. Exp. Biol. Med., 129, 268-273 (1968).
62. C. M. King and B. Phillips, Enzyme-catalyzed reactions of the carcinogen N-hydroxy-2-fluorenylacetamide with nucleic acid, Science, 159, 1351-1353 (1968).
63. J. R. DeBaun, J. Y. R. Smith, E. C. Miller, and J. A. Miller, Reactivity in vivo of the carcinogen N-hydroxy-2-acetylaminofluorene: Increase by sulfate ion, Science, 167, 184-186 (1970).
64. J. R. DeBaun, E. C. Miller, and J. A. Miller, N-Hydroxy-2-acetylaminofluorene sulfotransferase: Its probable role in carcinogenesis and protein-(methion-S-yl) binding in rat liver, Cancer Res., 30, 577-595 (1970).
65. J. A. Miller and E. C. Miller, The metabolic activation of carcinogenic aromatic amines and amides, Prog. Exp. Tumor Res., 11, 273-301 (1969).
66. H. Bartsch and E. Hecker, On the metabolic activation of the carcinogen N-hydroxy-N-2-acetylaminofluorene. III. Oxidation with horseradish peroxidase to yield 2-nitrosofluorene and N-acetoxy-N-2-acetylaminofluorene, Biochim. Biophys. Acta, 237, 567-578 (1971).
67. H. Bartsch, J. A. Miller, and E. C. Miller, N-Acetoxy-N-acetylaminoarenes and nitrosoarenes. One-electron non-enzymatic and enzymatic oxidation products of various carcinogenic aromatic acethydroxamic acids, Biochim. Biophys. Acta, 273, 40-51 (1972).
68. H. Bartsch, M. Dworkin, J. A. Miller, and E. C. Miller, Electrophilic N-acetoxyaminoarenes derived from carcinogenic N-hydroxy-N-acetylaminoarenes by enzymatic deacetylation and transacetylation in liver, Biochim. Biophys. Acta, 286, 272-298 (1972).
69. C. M. King and W. T. Allaben, Arylhydroxamic acid acetyltransferase, in Enzymatic Basis of Detoxication (W. B. Jakoby, ed.), Academic Press, New York, 1980, Vol. 2, pp. 187-197.
70. E. Kriek, On the interactions of N-2-fluorenylhydroxyamine with nucleic acids in vitro, Biochem. Biophys. Res. Commun., 20, 793-799 (1965).
71. M. Tada and M. Tada, Seryl-tRNA synthetase and activation of the carcinogen 4-nitroquinoline 1-oxide, Nature (London), 255, 510-512 (1975).
72. J. A. Miller and E. C. Miller, Metabolic action of carcinogenic aromatic amines and amides via N-hydroxylation and N-hydroxy esterification and its relationship to ultimate carcinogens as electrophilic reactants, Jerusalem Symp. Quantum Chem. Biochem., 1, 237-261 (1969).
73. P. N. Magee, R. Montesano, and R. Preussmann, N-Nitroso compounds and related carcinogens, ACS Monogr., 173, 491-625 (1976).
74. A. R. Mattocks, Toxicity of pyrrolizidine alkaloids, Nature (London), 217, 723-728 (1968).
75. C. C. J. Culvenor, D. T. Downing, J. A. Edgar, and M. V. Jago, Pyrrolizidine alkaloids as alkylating and antimitotic agents, Ann. N.Y. Acad. Sci., 163, 837-847 (1969).
76. H. V. Gelboin, A microsome-dependent binding of benzo[a]pyrene to DNA, Cancer Res., 29, 1272-1276 (1969).
77. P. L. Grover and P. Sims, Enzyme-catalyzed reactions of polycyclic hydrocarbons with deoxyribonucleic acid and protein in vitro, Biochem. J., 110, 159-160 (1969).
78. E. S. Reynolds, Liver parenchymal cell injury. IV. Pattern of incorporation of carbon and chlorine from carbon tetrachloride into chemical constituents in vivo, J. Pharmacol. Exp. Ther., 155, 117-126 (1967).
79. T. C. Butler, Reduction of carbon tetrachloride in vivo and reduction of carbon tetrachloride and chloroform in vitro by tissue and tissue constituents, J. Pharmacol. Exp. Ther., 134, 311-319 (1961).
80. P. Sims, P. L. Grover, A. Swaisland, K. Pal, and A. Hewer, Metabolic activation of benzo[a]pyrene proceeds by a diol-epoxide, Nature (London), 252, 326-328 (1974).
81. D. M. Jerina, J. M. Sayer, D. R. Thakker, H. Yagi, W. Levin, A. W. Wood, and A. H. Conney, Carcinogenicity of polycyclic aromatic hydrocarbons: The bay-region theory, in Carcinogenesis: Fundamental Mechanisms and Environmental Effects (B. Pullman, P. O. P. Ts'o, and H. Gelboin, eds.), Reidel Publ., Dordrecht, 1980, pp. 1-12.
82. E. G. Rogan, P. D. Devanesan, N. V. S. RamaKrishna, S. H. Higginbottom, N. S. Padmavathi, K. Chapman, E. L. Cavalieri, H. Jeong, R. Jankowiak, and G. J. Small, Identification and quantification of benzo[a]pyrene-DNA adducts formed in mouse skin, Chem. Res. Toxicol., 6, 356-363 (1993).
83. D. Chakravarti, J. C. Pelling, E. L. Cavalieri, and E. G. Rogan, Relating aromatic hydrocarbon-induced DNA adducts and c-H-ras mutations in mouse skin papillomas: The role of apurinic sites, Proc. Natl. Acad. Sci. USA, 92, 10422-10426 (1995).
84. 2 to rat liver DNA and microsomal RNA in vivo, Cancer Res., 37, 172-181 (1977).
85. 1 causes guanine substitution in nucleic acids, Nature (London), 267, 863-865 (1977).
86. 1-DNA or -RNA adducts formed in hepatic microsome-mediated reactions and in rat liver in vivo, Cancer Res., 37, 4430-4438 (1977).
87. 1 in vitro, Proc. Natl. Acad. Sci. USA, 74, 1870-1874 (1977).
88. F. Zadela, A. Croisy, A. Barbin, C. Malavielle, L. Tomatis, and H. Bartsch, Carcinogenicity of chloroethylene oxide, an ultimate reactive metabolite of vinyl chloride and bis(chlrormethyl)ether after subcutaneous administration and in initiation-promotion experiments in mice, Cancer Res., 40, 352-356 (1980).
89. E. Scherer, A. P. Steward, and P. Emmelot, Formation of precancerous islands in rat liver and modification of DNA by ethyl carbamate: Implications for its metabolism, Dev. Toxicol. Environ. Sci., 8, 249-254 (1980).
90. 14C]ethyl carbamate (urethan), Carcinogenesis, 3, 539-546 (1982).
91. 6-Ethenoadenosine formation, mutagenicity, and murine tumor induction as indicators of the generation of an electrophilic epoxide metabolite of the closely related carcinogens ethyl carbamate (urethene) and vinyl carbamate, Carcinogenesis, 11, 463-473 (1990).
92. K.-K. Park, Y.-J. Surh, B. C. Stewart, and J. A. Miller, Synthesis and properties of vinyl carbamate epoxide, a possible ultimate electrophilic and carcinogenic metabolite of vinyl carbamate and ethyl carbamate, Biochem. Biophys. Res. Commun., 169, 1094-1098 (1990).
93. K.-K. Park, A. Liem, B. C. Stewart, and J. A. Miller, Vinyl carbamate epoxide, a major strong electrophilic, mutagenic, and carcinogenic metabolite of vinyl carbamate and ethyl carbamate (urethane), Carcinogenesis, 74, 441-450 (1993).
94. 6-atom of adenine residues as sites for covalent binding of metabolically activated 1′-hydroxysafrole to mouse liver DNA in vivo, Cancer Res., 41, 2664-2671 (1981).
95. D. H. Phillips, J. A. Miller, E. C. Miller, and B. Adams, Structures of the DNA adducts formed in mouse liver after administration of the proximate carcinogen 1′-hydroxy estragole, Cancer Res., 41, 176-181 (1981).
96. E. W. Boberg, E. C. Miller, J. A. Miller, and A. Poland, Strong evidence from studies with brachymorphic mice and pentachlorophenol that 1′-sulfooxysafrole is the major electrophilic and carcinogenic metabolite of 1′-hydroxysafrole in mouse liver, Cancer Res., 43, 5163-5173 (1983).
97. Y.-J. Surh, C.-C. Lai, J. A. Miller, and E. C. Miller, Hepatic DNA and RNA adduct formation from the carcinogen 7-hydroxymethyl-12-methylbenz[a]anthracene and its electrophilic sulfuric acid ester metabolite in preweanling rats and mice, Biochem. Biophys. Res. Commun., 144, 576-582 (1987).
98. Y.-J. Surh, A. Liem, E. C. Miller, and J. A. Miller, Metabolic activation of 6-hydroxymethylbenzo[a]pyrene: Formation of an electrophilic sulfuric acid ester and benzylic DNA adducts in rat liver in vivo and in reactions in vitro, Carcinogenesis, 10, 1519-1528 (1989).
99. 1 mice, Biochem. Biophys. Res. Commun., 172, 85-91 (1990).
100. Y. -J. Surh, A. Liem, E. C. Miller, and J. A. Miller, 7-Sulfooxymethyl-12-methylbenz[a]anthracene is an electrophilic mutagen, but does not appear to play a role in carcinogenesis by 7,12-dimethylbenz[a]anthracene or 7-hydroxymethyl-12-methylbenz[a]anthracene, Carcinogenesis, 12, 299-347 (1991).
101. R. R. Snyder, C. M. Widmer, D. J. Jollow, G. M. Kalf, J. J. Kocsis et al. (eds.), Biological Reactive Species, Molecular and Cellular Effects and Their Impact on Human Health, Advances in Experimental Medicine and Biology Vois. I, IIA, IIB, III, and IV, Plenum Press, New York, 1977, 1982, 1985, 1991.
102. L. A. Loeb and R. A. Zakour, Metals and genetic miscoding, in Nucleic Acid-Metal Ion Interactions (T. G. Spiro, ed.), Wiley, New York, 1980, pp. 115-144.
103. W. C. J. Ross, Biological Alkylating Agents, Butterworth, London, 1962.
104. C. C. Price, G. M. Gaucher, P. Koneru, R. Shibakawa, J. R. Sows, and M. Yamaguchi, Mechanisms of action of alkylating agents, Ann. N.Y. Acad. Sci., 163, 593-598 (1969).
105. V. M. Maher, E. C. Miller, J. A. Miller, and W. Szybalski, Mutations and decreases in density of transforming DNA produced by derivatives of the carcinogens 2-acetylaminofluorene and N-methyl-4-aminoazobenzene, Molec. Pharmacol., 4, 411-426 (1968).
106. A. Hollaender and F. J. deSerres (eds.), in Chemical Mutagens: Principles and Methods for their Detection, Plenum, New York, 1971-1982, Vols. 1-7.
107. B. N. Ames, W. E. Durston, E. Yamasaki, and F. D. Lee, Carcinogens are mutagens: A simple test system combining liver homogenates for activation and bacteria for detection, Proc. Natl. Acad. Sci. USA, 70, 2281-2285 (1973).
108. B. N. Ames, J. McCann, and E. Yamasaki, Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test, Mutat. Res., 31, 347-364 (1975).
109. B. A. Fetterman, B. S. Kim, B. H. Margolin, J. S. Schildcrout, M. G. Smith, S. M. Wagner, and E. Zeiger, Predicting rodent carcinogenicity from mutagenic potency measured in the Ames Salmonella assay, Environ. Molec. Mutagen., 29, 312-322 (1997).
110. H. C. Pilot, Fundamentals of Oncology, 3rd ed., Marcel Dekker, Inc., New York, 1986.
111. H. C. Pitot, Y. P. Dragan, J. Teeguarden, S. Hsia, and H. Campbell, Quantitation of multistage carcinogenesis in rat liver, Toxicol. Pathol., 24, 119-128 (1996).