Molecular Mechanisms in Protection Against Carcinogenesis

  • Paul Talalay
  • Mary J. De Long
  • Hans J. Prochaska


The view that the overwhelming majority of human cancers are preventable is as widely accepted today as was the previously held conviction that cancer is an inevitable concomitant of the aging process. Epidemiological studies have led to this revision of our views of the causes of cancer and the prospects for its prevention (1). Because the effective treatment of established, and especially of disseminated, malignancies remains a recalcitrant problem in which progress is debatable (2,3), the development of protective measures against the development of cancer is a compelling goal.


Polycyclic Aromatic Hydrocarbon Phenolic Antioxidant Quinone Reductase Aromatic Diamine Polycyclic Hydrocarbon 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.







7,12-dimethylbenz(a)anthracene; ethoxyquin, 1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline; quinone reductase


(quinone acceptor) oxidoreductase (EC, also known as menadione reductase, DT diaphorase, or vitamin K reductase.


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  1. 1.
    R. Doll and R. Peto, The Causes of Cancer: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today, J. Nat. Cancer Inst. 66: 1191 (1981).PubMedGoogle Scholar
  2. 2.
    J. Cairns, The Treatment of Diseases and the War Against Cancer, Sci. Am. 253: 51 (1985).PubMedCrossRefGoogle Scholar
  3. 3.
    E. Frei, III, Curative Cancer Chemotherapy, Cancer Res. 45: 6523 (1985).PubMedGoogle Scholar
  4. 4.
    P. Talalay, The Future of Medicine: Are We Prepared? in: “Twenty-first Century Prospects and Problems,” K. H. Kim, ed., Kyung Hee University Press, Seoul, (1979).Google Scholar
  5. 5.
    L. W. Wattenberg, Inhibition of Neoplasia by Minor Dietary Constituents, Cancer Res. 43: 2448s (1983).Google Scholar
  6. 6.
    L. W. Wattenberg, Chemoprevention of Cancer, Cancer Res. 45: 1 (1985).PubMedCrossRefGoogle Scholar
  7. 7.
    G. Rosen, “A History of Public Health,” ND Monographs on Medical History, MD Publications, New York (1958).CrossRefGoogle Scholar
  8. 8.
    S. Pell and W. E. Fayerweather, Trends in the Incidence of Myocardial Infarction and in Associated Mortality and Morbidity in a Large Employed Population, N. Eng. J. Med. 312: 1005 (1985).CrossRefGoogle Scholar
  9. 9.
    I. Berenblum, The Modifying Influence of Dichloroethyl Sulphide on the Induction of Tumors in Mice by Tar, J. Path. Bact. 32: 425 (1929).CrossRefGoogle Scholar
  10. 10.
    I. Berenblum, The Anti-carcinogenic Action of Dichlorodiethyl Sulphide (Mustard Gas), J. Path. Bact. 34: 731 (1931).CrossRefGoogle Scholar
  11. 11.
    S. P. Reimann and E. M. Hall, Protective Action of Sulfhydryl Against Carcinogenesis Induced with 1,2,5,6-di-Benzanthracene, Arch. Pathol. 22: 55 (1936).Google Scholar
  12. 12.
    A. Lacassagne, Buu-Hoi, and G. Rudali, Induction of the Carcinogenic Action Produced by a Weakly Carcinogenic Hydrocarbon on a Highly Active Carcinogenic Hydrocarbon, Brit. J. Exp. Pathol. 24: 5 (1945).Google Scholar
  13. 13.
    B. Riegel, W. B. Wartman, W. T. Hill, B. B. Reeb, P. Shubik, and D. W. Stanger, Delay of Methylcholanthrene Skin Carcinogenesis in Mice by 1,2,5,6-Dibenzofluorene, Cancer Res. 11: 301 (1951).PubMedGoogle Scholar
  14. 14.
    H. L. Richardson and L. Cunningham, The Inhibitory Action of Methylcholanthrene on Rats Fed the Azo Dye 3’-Methyl-4-dimethyl-aminoazobenzene, Cancer Res. 11: 274 (1951).Google Scholar
  15. 15.
    H. L. Richardson and E. Borsos-Nachtnebel, Study of Liver Tumor Development and Histologic Changes in Other Organs in Rats Fed Azo Dye 3’-Methyl-4-dimethylaminoazobenzene, Cancer Res. 11: 398 (1951).PubMedGoogle Scholar
  16. 16.
    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 (1952).PubMedGoogle Scholar
  17. 17.
    J. A. Miller and E. C. Miller, The Carcinogenic Aminoazo Dyes, Adv. Cancer Res. 1: 339 (1953).PubMedCrossRefGoogle Scholar
  18. 18.
    A. H. Conney, G. C. Mueller, and J. A. Miller, The Metabolism of Methylated Amino Azo Dyes. V. Evidence for the Induction of Enzyme Synthesis in the Rat by 3-Methylcholanthrene, Cancer Res. 16: 450 (1956).PubMedGoogle Scholar
  19. 19.
    E. C. Miller, J. A. Miller, R. R. Brown, and J. C. MacDonald, On Protective Action of Certain Polycyclic Aromatic Hydrocarbons Against Carcinogenesis by Aminoazo Dyes and 2-Acetylaminofluorene, Cancer Res. 18: 469 (1958).PubMedGoogle Scholar
  20. 20.
    E. C. Miller and J. A. Miller, Searches for Ultimate Chemical Carcinogens and Their Reactions with Cellular Macromolecules, in: “Accomplishments in Cancer Research,” J. G. Fortner and J. E. Rhoads, eds., Lippincott, Philadelphia (1980).Google Scholar
  21. 21.
    E. C. Miller and J. A. Miller, Some Historical Perspectives on the Metabolism of Xenobiotic Chemicals to Reactive Electrophiles, in: Bioactivation of Foreign Compounds,“ M. W. Anders, ed., Academic Press, Orlando (1985).Google Scholar
  22. 22.
    C. W. Welsch, Host Factors Affecting the Growth of Carcinogen-induced Rat Mammary Carcinomas: A Review and Tribute to Charles Brenton Huggins, Cancer Res. 45: 3415 (1985).PubMedGoogle Scholar
  23. 23.
    C. B. Huggins, “Experimental Leukemia and Mammary Cancer. Induction, Prevention, Cure,” The University of Chicago Press, Chicago (1979).Google Scholar
  24. 24.
    H. G. Williams-Ashman and C. Huggins, Oxydation of Reduced Pyridine Nucleotides in Mammary Gland and Adipose Tissue Following Treatment with Polynuclear Hydrocarbons, Medicina Experimentalis 4: 223 (1961).PubMedGoogle Scholar
  25. 25.
    C. Huggins and R. Fukunishi, Induced Protection of Adrenal Cortex Against 7,12-Dimethylbenz(a)anthracene. Influence of Ethionine Induction of Menadione Reductase. Incorporation of Thymidine- H, J. Exptl. Med. 119: 923 (1964).CrossRefGoogle Scholar
  26. 26.
    C. Huggins and J. Pataki, Aromatic Azo Derivatives Preventing Mammary Cancer and Adrenal Injury from 7,12-Dimethylbenz(a)anthracene, Proc. Natl. Acad. Sci. U.S.A. 53: 791 (1965).PubMedCrossRefGoogle Scholar
  27. 27.
    C. B. Huggins, N. Ueda, and A. Russo, Azo Dyes Prevent Hydrocarbon-induced Leukemia in the Rat, Proc. Natl. Acad. Sci. U.S.A. 75: 4524 (1978).PubMedCrossRefGoogle Scholar
  28. 28.
    Y. Ito, S. Maeda, T. Fujihara, N. Ueda, and T. Sugiyama, Suppression of 7,12-Dimethylbenz(a)anthracene-induced Chromosome Aberrations in Rat Bone Marrow Cells after Treatment with Sudan III and Related Azo Dyes, J. Nat. Cancer Inst. 69: 1343 (1982).PubMedGoogle Scholar
  29. 29.
    Y. Ito, S. Maeda, K. Souno, N. Ueda, and T. Sugiyama, Induction of Hepatic Glutathione Transferase and Suppression of 7,12-Dimethylbenz(a)anthracene-induced Chromosome Aberrations in Rat Bone Marrow Cells after Treatment with Sudan III and Related Azo Dyes, J. Nat. Cancer Inst. 73: 177 (1984).PubMedGoogle Scholar
  30. 30.
    O. S. Frankfurt, L. P. Lipchina, T. V. Bunto, and N. M. Emanuel, Effect of 4-Methyl-2.6-di-tert-butylphenol(Ionol) on Induction of Liver Tumors in Rats, Byull. Eksp. Biol. Med. (USSR) 64: 86 (1967).Google Scholar
  31. 31.
    L. W. Wattenberg, Inhibitors of Chemical Carcinogenesis, Adv. Cancer Res. 26: 197 (1978).PubMedCrossRefGoogle Scholar
  32. 32.
    L. W. Wattenberg and L. K. T. Lam, Inhibition of Chemical Carcinogenesis by Phenols, Coumarins, Aromatic Isothiocyanates, Flavones, and Indoles, in: “Inhibition of Tumor Induction and Development,” M. S. Zedeck and M. Lipkin, eds., Plenum Press, New York (1981).Google Scholar
  33. 33.
    R. Kahl, Synthetic Antioxidants: Biochemical Actions and Interference with Radiation, Toxic Compounds, Chemical Mutagens and Chemical Carcinogens, Toxicology 33: 185 (1984).PubMedCrossRefGoogle Scholar
  34. 34.
    M. S. Zedeck and M. Lipkin, eds., “Inhibition of Tumor Induction and Development,” Plenum Press, New York (1981).Google Scholar
  35. 35.
    T. J. Slaga and W. M. Bracken, The Effects of Antioxidants on Skin Tumor Initiation and Aryl Hydrocarbon Hydroxylase, Cancer Res. 37: 1631 (1977).PubMedGoogle Scholar
  36. 36.
    T. W. Kensler, D. M. Bush, and W. J. Kozumbo, Inhibition of Tumor Promotion by a Biomimetic Superoxide Dismutase, Science 221: 75 (1983).PubMedCrossRefGoogle Scholar
  37. 37.
    W. J. Kozumbo, J. L. Seed, and T. W. Kensler, Inhibition by 2(3)-tertButyl-4-hydroxyanisole and Other Antioxidants of Epidermal Ornithine Decarboxylase Activity Induced by 12–0-Tetradecanoylphorbol-13acetate, Cancer Res. 43: 2555 (1983).PubMedGoogle Scholar
  38. 38.
    L. A. Cohen, M. Polansky, K. Furuya, M. Reddy, B. Berke, and J. H. Weisburger, Inhibition of Chemically-induced Mammary Carcinogenesis in Rats by Short-term Exposure to Butylated Hydroxytoluene (BHT): Interrelationships among BHT Concentrations, Carcinogen Dose and Diet, J. Nat. Cancer Inst. 72: 165 (1984).PubMedGoogle Scholar
  39. 39.
    H. A. Dunsford, P. M. Dolan, J. L. Seed, and E. Bueding, Effects of Multiple Putative Anticarcinogens on the Carcinogenicity of trans5-Amino-3-[2-(5-nitro-2-furyl)vinyl]-1,2,4-oxadiazole, J. Nat. Cancer Inst. 73: 161 (1985).Google Scholar
  40. 40.
    J. L. Speier, L. K. T. Lam, and L. W. Wattenberg, Effects of Administration to Mice of Butylated Hydroxyanisole by Oral Intubation on Benzo(a)pyrene-induced Pulmonary Adenoma Formation and Metabolism of Benzo(a)pyrene, J. Nat. Cancer Inst. 60: 605 (1978).PubMedGoogle Scholar
  41. 41.
    L. K. T. Lam, A. V. Fladmoe, J. B. Hochalter, and L. W. Wattenberg, Short Time Interval Effects of Butylated Hydroxyanisole on the Metabolism of Benzo(a)pyrene, Cancer Res. 40: 2824 (1980).PubMedGoogle Scholar
  42. 42.
    A. M. Benson, R. P. Batzinger, S.-Y. L. Ou, E. Bueding, Y.-N. Cha, and P. Talalay, Elevation of Hepatic Glutathione S-transferase Activities and Protection Against Mutagenic Metabolites of Benzo(a)pyrene by Dietary Antioxidants, Cancer Res. 38: 4486 (1978).PubMedGoogle Scholar
  43. 43.
    A. H. Conney, Pharmacological. Implications of Microsomal Enzyme Induction, Pharmacol. Rev. 19: 317 (1967).PubMedGoogle Scholar
  44. 44.
    J. L. Speier, and L. W. Wattenberg, Alterations in Microsomal Metabolism of Benzo(a)pyrene in Mice Fed Butylated Hydroxyanisole, J. Nat. Cancer Inst. 55: 469 (1975).PubMedGoogle Scholar
  45. 45.
    Y.-N. Cha and E. Bueding, Effects of 2(3)-tert-4-Butyl-4-hydroxyanisole Administration on the Activities of Several Hepatic Microsomal and Cytoplasmic Enzymes in Mice, Biochem. Pharm. 28: 1917 (1979).PubMedCrossRefGoogle Scholar
  46. 46.
    A. D. Rahimtula, B. Jernstrom, L. Dock, and P. Moldeus, Effects of Dietary and in vitro 2(3)-t-Butyl-4-hydroxyanisole and Other Phenols on Hepatic Enzyme Activities in Mice, Br. J. Cancer 45: 935 (1982).PubMedCrossRefGoogle Scholar
  47. 47.
    F.-L. Chung, M. Wang, S. G. Carmella, and S. S. Hecht, Effects of Butylated Hydroxyanisole on the Tumorigenicity and Metabolism of N-Nitrosodimethylamine and N-Nitrosopyrrolidine in A/J Mice, Cancer Res. 46: 165 (1986).PubMedGoogle Scholar
  48. 48.
    W. Sydor, Jr., M. W. Chou, S. K. Yang, and C. S. Yang, Regioselective Inhibition of Benzo(a)pyrene Metabolism by Butylated Hydroxyanisole, Carcinogenesis 4: 703 (1983).CrossRefGoogle Scholar
  49. 49.
    R. P. Batzinger, S.-Y. L. Ou, and E. Bueding, Antimutagenic Effects of 2(3)-tert-Butyl-4-hydroxyanisole and of Antimicrobial Agents, Cancer Res. 38: 4478 (1978).PubMedGoogle Scholar
  50. 50.
    A. M. Benson, Y.-N. Cha, E. Bueding, H. S. Heine, and P. Talalay, Elevation of Extrahepatic Glutathione S-transferase and Epoxide Hydratase Activities by 2(3)-tert-Butyl-4-hydroxyanisole, Cancer Res. 39: 2971 (1979).PubMedGoogle Scholar
  51. 51.
    A. M. Benson, M. J. Hunkeler, and P. Talalay, Increase of NAD(P)H:quinone reductase by Dietary Antioxidants: Possible Role in the Protection Against Carcinogenesis and Toxicity, Proc. Natl. Acad. Sci. U.S.A. 77: 5216 (1980).PubMedCrossRefGoogle Scholar
  52. 52.
    P. Talalay, R. P. Batzinger, A. M. Benson, E. Bueding, and Y.-N. Cha, Biochemical Studies on the Mechanisms by Which Dietary Antioxidants Suppress Mutagenic Activity, Adv. Enz. Reg. 17: 23 (1979).CrossRefGoogle Scholar
  53. 53.
    W. R. Pearson, J. J. Windle, J. F. Morrow, A. M. Benson, and P. Talalay, Increased Synthesis of Glutatione S-transferase in Response to Anticarcinogenic Antioxidants. Cloning and Measurement of Messenger RNA, J. Biol. Chem. 258: 2052 (1983).PubMedGoogle Scholar
  54. 54.
    V. L. Sparnins, P. L. Venegas, and L. W. Wattenberg, Glutathione Stransferase Activity: Enhancement by Compounds Inhibiting Chemical Carcinogenesis and by Dietary Constituents, J. Nat. Cancer Inst. 68: 493 (1982).PubMedGoogle Scholar
  55. 55.
    A. M. Benson and P. B. Barretto, Effects of Disulfiram, Diethyl-dithiocarbamate, Bisethylxanthogen, and Benzyl Isothiocyanate on Glutathione Transferase Activities in Mouse Organs, Cancer Res. 45: 4219 (1985).PubMedGoogle Scholar
  56. 56.
    T. W. Kensler, P. A. Egner, M. A. Trush, E. Bueding, and J. D. Groopman, Modification of Alflatoxin B1 Binding to DNA in vivo in Rats Fed Phenolic Antioxidants, Ethoxyquin and a Dithiothione, Carcinogenesis 6: 759 (1985).PubMedCrossRefGoogle Scholar
  57. 57.
    L. W. Wattenberg and L. K. T. Lam, Protective Effects of Coffee Constituents on Carcinogenesis in Experimental Animals, in: “Coffee and Health,” Banbury Report No. 17, B. MacMahon and T. Sugimura, eds., Cold Spring Harbor Laboratory, Cold Spring Harbor, (1984).Google Scholar
  58. 58.
    L. W. Wattenberg, Inhibition of Carcinogenic and Toxic Effects of Polycyclic Hydrocarbons by Phenolic Antioxidants and Ethoxyquin, J. Nat. Cancer Inst. 48: 1425 (1972).PubMedGoogle Scholar
  59. 59.
    S. S. Ansher, P. Dolan, and E. Bueding, Chemoprotective Effects of Two Dithiolthiones and of Butylhydroxyanisole against Carbon Tetrachloride and Acetaminophen Toxicity, Hepatology 3: 932 (1983).PubMedCrossRefGoogle Scholar
  60. 60.
    C. L. Miranda, M. C. Henderson, and D. R. Buhler, Dietary Butylated Hydroxyanisole Reduces Covalent Binding of Acetaminophen to Mouse Tissue Proteins In Vivo, Toxicol. Lett. 25: 89 (1985).PubMedCrossRefGoogle Scholar
  61. 61.
    Y. M. Ioannou, A. G. E. Wilson, and M. W. Anderson, Effect of Butylated Hydroxyanisole, a-Angelicalactone, and -Naphthoflavone on Benzo(a)pyrene:DNA-adduct Formation In Vivo in the Forestomach, Lung and Liver of Mice, Cancer Res. 42: 1199 (1982).PubMedGoogle Scholar
  62. 62.
    H. Thor, M. T. Smith, P. Hartzell, G. Bellomo, S. A. Jewell, and S. Orrenius, The Metabolism of Menadione (2-methyl-1,4-naphthoquinone) by Isolated Hepatocytes. A Study of the Implications of Oxidative Stress in Intact Cells, J. Biol. Chem. 257: 12419 (1982).PubMedGoogle Scholar
  63. 63.
    H. Wefers, T. Komai, P. Talalay, and H. Sies, Protection Against Reactive Oxygen Species by NAD(P)H:quinone Reductase Induced by the Dietary Antioxidant Butylated Hydroxyanisole (BHA). Decreased Hepatic Low-level Chemiluminescence during Quinone Redox Cycling, FEBS Lett. 169: 63 (1984).PubMedCrossRefGoogle Scholar
  64. 64.
    R. G. Harvey, Activated Metabolites of Carcinogenic Hydrocarbons, Acct. Chem. Res. 14: 218 (1981).CrossRefGoogle Scholar
  65. 65.
    M. J. Long, H. J. Prochaska, and P. Talalay, Substituted Phenols as Inducers of Enzymes that Inactivate Electrophilic Compounds, in: “Protective Agents in Cancer,” D. C. H. McBrien and T. F. Slater, eds., Academic Press, London (1983).Google Scholar
  66. 66.
    M. J. De Long, H. J. Prochaska, and P. Talalay, Tissue-specific Induction Patterns of Cancer-protective Enzymes in Mice by tert-Butyl-4hydroxyanisole and Related Substituted Phenols, Cancer Res. 45: 546 (1985).PubMedGoogle Scholar
  67. 67.
    H. J. Prochaska, H. S. Bregman, M. J. De Long, and P. Talalay, Specificity of Induction of Cancer Protective Enzymes by Analogues of tertButyl-4-hydroxyanisole (BHA), Biochem. Pharm. 34: 3909 (1985).PubMedCrossRefGoogle Scholar
  68. 68.
    M. J. De Long, H. J. Prochaska, and P. Talalay, Induction of NAD(P)H:quinone Reductase in Murine Hepatoma Cells by Phenolic Antioxidants, Azo Dyes, and Other Chemoprotectors: A Model System for the Study of Anticarcinogens, Proc. Natl. Acad. Sci. U.S.A 83: 787 (1986).PubMedCrossRefGoogle Scholar
  69. 69.
    H. P. Bernhard, G. J. Darlington, and F. H. Ruddle, Expression of Liver Phenotypes in Cultured Mouse Hepatoma Cells: Synthesis and Secretion of Serum Albumin, Develop. Biol. 35: 83 (1973).PubMedCrossRefGoogle Scholar
  70. 70.
    G. J. Darlington, H. P. Bernhard, R. A. Miller, and F. H. Ruddle, Expression of Liver Phenotypes in Cultured Mouse Hepatoma Cells, J. Nat. Cancer. Inst. 64: 809 (1980).PubMedGoogle Scholar
  71. 71.
    O. Hankinson, Single Step Selection of Clones of a Mouse Hepatoma Line Deficient in Aryl Hydrocarbon Hydroxylase, Proc. Natl. Acad. Sci. U.S.A 76: 373 (1979).PubMedCrossRefGoogle Scholar
  72. 72.
    W. F. Benedict, J. E. Gielen, I. S. Owens, A. Niwa, and D. W. Nebert, Aryl Hydrocarbon Hydroxylase Induction in Mammalian Liver Cell Culture. IV. Stimulation of the Enzyme Activity in Established Cell Lines Derived from Rat or Mouse Hepatoma and from Normal Rat Liver, Biochem. Pharm. 22: 2766 (1973).PubMedCrossRefGoogle Scholar
  73. 73.
    G. S. Duthu, M. S. Nestor, J. A. Berliner, R. M. Philpot, and O. Hankinson, Characterization of NADPH-cytochrome P-450 Reductase in a Mouse Hepatoma Cell Line, Cancer Lett. 18: 237 (1983).PubMedCrossRefGoogle Scholar
  74. 74.
    G. S. Duthu and O. Hankinson, The Defects in All Classes of Aryl Hydrocarbon Hydroxylase Deficient Mutants of Mouse Hepatoma Line, Hepa-1, are Restricted to Activities Catalyzed by Cytochrome P-450, Cancer Lett. 20: 249 (1983).PubMedCrossRefGoogle Scholar
  75. 75.
    D. I. Israel, M. G. Estalano, D. R. Galeazzi, and J. P. Whitlock, Jr., Superinduction of Cytochrome P1–450 Gene Transcription by Inhibition of Protein Synthesis in Wild Type and Variant Mouse Hepatoma Cells, J. Biol. Chem. 260: 5648 (1985).PubMedGoogle Scholar
  76. 76.
    B. N. Ames, Dietary Carcinogens and Anticarcinogens. Oxygen Radicals and Degenerative Diseases, Science 221: 1256 (1983).Google Scholar
  77. 77.
    C. Lind, P. Hochstein, and L. Ernster, DT-diaphorase as a Quinone Reductase: A Cellular Control Device Against Semiquinone and Superoxide Radical Formation, Arch. Biochem. Biophys. 216: 178 (1982).PubMedCrossRefGoogle Scholar
  78. 78.
    P. L. Chesis, D. E. Levin, M. T. Smith, L. Ernster, and B. N. Ames, Mutagenicity of Quinones: Pathways of Metabolic Activation and Detoxification, Proc. Natl. Acad. Sci. U.S.A. 81: 1696 (1984).PubMedCrossRefGoogle Scholar
  79. 79.
    H. Morrison, B. Jernstrom, M. Nordenskjold, H. Thor, and S. Orrenius, Induction of DNA Damage by Menadione (2-methyl-1,4-naphthoquinone) in Primary Cultures of Rat Hepatocytes, Biochem. Pharm. 33: 1763 (1984).PubMedCrossRefGoogle Scholar
  80. 80.
    H. Kappus and H. Sies, Toxic Drug Effects Associated with Oxygen Metabolism: Redox Cycling and Lipid Peroxidation, Experientia 37: 1233 (1981).PubMedCrossRefGoogle Scholar
  81. 81.
    T. Iyanagi and I. Yamazaki, One-Electron Transfer Reactions in Biochemical Systems. V. Difference in Mechanism of Quinone Reduction by the NADH Dehydrogenase and the NAD(P)H Dehydrogenase (DT-diaphorase), Biochim. Biophys. Acta 216: 282 (1970).PubMedCrossRefGoogle Scholar
  82. 82.
    C. Lind. H. Vadi, and L. Ernster, Metabolism of Benzo(a)pyrene-3,6quinone and 3-Hydroxybenzo(a)pyrene in Liver Microsomes from 3Methylcholanthrere-treated Rats, Arch. Biochem. Biophys. 190: 97 (1978).PubMedCrossRefGoogle Scholar
  83. 83.
    C. Lind, Relationship between the Rate of Reduction of Benzo(a)pyrene3,6-quinone and the Formation of Benzo(a)pyrene-3,6-quinol Glucuronides in Rat Liver Microsomes, Biochem. Pharm. 34: 895 (1985).PubMedCrossRefGoogle Scholar
  84. 84.
    P. Talalay and A. M. Benson, Elevation of Quinone Reductase Activity by Anticarcinogenic Antioxidants, Adv. Enz. Reg. 20: 287 (1982).CrossRefGoogle Scholar
  85. 85.
    G. J. Smith, K. Huebner, and G. Litwack, Expression of Ligandin and Glutathione S-transferase Activities by Cells in Tissue Culture, Biochem. Biophys. Res. Comm. 76: 1174 (1977).PubMedCrossRefGoogle Scholar
  86. 86.
    H. J. Prochaska, M. J. De Long, and P. Talalay, On the Mechanism of Induction of Cancer-protective Enzymes: A Unifying Proposal, Proc. Natl. Acad. Sci. U.S.A. 82: 8232 (1985).PubMedCrossRefGoogle Scholar
  87. 87.
    R. El-Rashidi and S. Niazi, A New Metabolite of Butylated Hydroxyanisole in Man, Biopharmaceutics Drug Disp. 4: 389 (1983).CrossRefGoogle Scholar
  88. 88.
    H. M. Hassan and I. Fridovich, Regulation of the Synthesis of Superoxide Dismutase in Escherichia coli. Induction by Methyl Viologen, J. Biol. Chem. 252: 7667 (1977).PubMedGoogle Scholar
  89. 89.
    H. M. Hassan and I. Fridovich, Intracellular Production of Superoxide Radical and of Hydrogen Peroxide by Redox Active Compounds, Arch. Biochem. Biophys. 196: 385 (1979).PubMedCrossRefGoogle Scholar
  90. 90.
    E. A. Craig, The Heat Shock Response, CRC Crit. Rev. Biochem. 18: 239 (1985).CrossRefGoogle Scholar
  91. 91.
    E. Witkin, Ultraviolet Mutagenesis and Inducible DNA Repair in Escherichia coli, Bacteriol. Rev. 40: 869 (1976).PubMedGoogle Scholar
  92. 92.
    R. L. Levine, Oxidative Modification of Glutamine Synthetase. I. Inactivation is Due to Loss of One Histidine Residue, J. Biol. Chem. 258: 11823 (1983).PubMedGoogle Scholar
  93. 93.
    R. L. Levine, C. N. Oliver, R. M. Fulks, and E. R. Stadtman, Turnover of Bacterial Glutamine Synthetase: Oxidative Inactivation Precedes Proteolysis, Proc. Natl. Acad. Sci. U.S.A. 78: 2120 (1981).PubMedCrossRefGoogle Scholar
  94. 94.
    L. W. Wattenberg, J. B. Coccia, and L. K. T. Lam, Inhibitory Effect of Phenolic Compounds on Benzo(a)pyrene-induced Neoplasia, Cancer Res. 40: 2820 (1980).PubMedGoogle Scholar
  95. 95.
    S. Fujita and J. Peisach, Liver Microsomal Cytochromes P-450 and Azoreductase Activity, J. Biol. Chem. 253: 4512 (1978).PubMedGoogle Scholar
  96. 96.
    A. Poland and J. C. Knutson, 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Related Halo-generated Aromatic Hydrocarbons: Examination of the Mechanism of Toxicity, Ann. Rev. Pharmacol. Toxicol. 22: 517 (1982).CrossRefGoogle Scholar
  97. 97.
    H. J. Eisen, R. R. Hannah, C. Legraverend, A. B. Okey, and D. W. Nebert, the Ah Receptor: Controlling Factor in the Induction of Drug-metabolizing Enzymes by Certain Chemical Carcinogens and Other Environmental Pollutants, in: “Biochemical Actions of Hormones,” Volume 10, G. Litwack, ed., Academic Press, New York (1983).Google Scholar
  98. 98.
    I. S. Owens, Genetic Regulation of UDP-glucuronosyltransferase Induction by Polycyclic Aromatic Compounds in Mice. Co-segregation with Aryl Hydrocarbon (benzo[a]pyrene) Hydroxylase Induction, J. Biol. Chem. 252: 2827 (1977).PubMedGoogle Scholar
  99. 99.
    K. Kumaki, N. M. Jensen, J. G. M. Shire, and D. W. Nebert, Genetic Differences in Induction of Cytosol Reduced-NAD(P):menadione Oxidoreductase and Microsomal Aryl Hydrocarbon Hydroxylase in the Mouse, J. Biol. Chem. 252: 157 (1977).PubMedGoogle Scholar
  100. 100.
    J. S. Felton, J. N. Ketley, W. B. Jakoby, A. Aitio, J. R. Bend, and D. W. Nebert, Hepatic Glutathione Transferase Activity Induced by Polycyclic Aromatic Compounds. Lack of Correlation with the Murine Ah Locus, Mol. Pharmacol. 18: 559 (1980).PubMedGoogle Scholar
  101. 101.
    R. T. Williams, Comparative Patterns of Drug Metabolism, Fed. Proc. 26: 1029 (1967).PubMedGoogle Scholar
  102. 102.
    F. P. Guengerich and D. C. Liebler, Enzymatic Activation of Chemicals to Toxic Metabolities, CRC Crit. Rev. Toxicol. 14: 259 (1985).CrossRefGoogle Scholar
  103. 103.
    M. J. Long, P. Dolan, A. B. Santamaria, and E. Bueding, 1,2-Dithiol3-thione Analogues: Effect on NAD(P)H:quinone Reductase and Glutathione Levels in Murine Hepatoma Cells, Carcinogenesis, in press (1986).Google Scholar

Copyright information

© Springer Science+Business Media New York 1987

Authors and Affiliations

  • Paul Talalay
    • 1
  • Mary J. De Long
    • 1
  • Hans J. Prochaska
    • 1
  1. 1.Department of Pharmacology and Experimental TherapeuticsThe Johns Hopkins University School of MedicineBaltimoreUSA

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