A major concern of molecular epidemiology is the identification of individuals at increased risk of cancer by obtaining evidence of high exposure to carcinogens that may lead to pathobiological lesions in target cells. DNA is considered to be a target for modification by mutagens and carcinogens; therefore, damage to DNA can be used as an internal, molecular dosimeter of carcinogen exposure. The reactive species of these carcinogens may bind either directly to DNA to form adducts or indirectly to cause secondary DNA lesions through free radicals and aldehydes. Highly sensitive and specific methods have been developed to measure DNA lesions and DNA repair products that are found in biological specimens from humans exposed to carcinogens in the environment. For example, DNA adducts have been measured in cells and tissues from people exposed environmentally to carcinogenic polycyclic aromatic hydrocarbons or alkylating agents. Antibodies recognizing carcinogen-DNA adducts have also been detected in human sera. Carcinogen-protein adducts are also being used as molecular dosimeters of carcinogen exposure. The advantages and limitations of the various methods used to measure carcinogen-macromolecular adducts are discussed here. The use of two or more complementary assays to obtain confirmatory results is recommended.
References
1.
1. Harris, C.C., Weston, A., Willey, J.C., Trivers, G.E., Mann, D.L. (1987). Biochemical and molecular epidemiology of human cancer: Indicators of carcinogen exposure, DNA damage, and genetic predisposition. Environ. Health Perspect.75, 109–119.
2.
2. Perera, F.P., and Weinstein, I.B. (1982). Molecular epidemiology and carcinogen-DNA adduct detection: New approaches to studies of human cancer causation. J. Chron. Dis.35, 581–600.
3.
3. Harris, C.C., Vahakangas, K., Autrup, H., Trivers, G.E., Shamsuddin, A.K.M., Trump, B.F., Boman, B.M., and Mann, D.L. (1985). Biochemical and molecular epidemiology of human cancer risk. In: Scarpelli, D., Craighead, J., and Kaufman, N., (eds). The Pathologist and the Environment.Baltimore: Williams & Wilkins, pp. 140–167.
4.
4. Harris, C.C. (1986). Biochemical and Molecular Epidemiology of Cancer.New York: Alan R. Liss.
5.
5. Autrup, H., and Harris, C.C. (1983). Metabolism of chemical carcinogens by cultured human tissues. In: Harris, C.C., and Autrup, H., (eds). Human Carcinogenesis.New York: Academic Press, pp. 169–194.
6.
6. Doll, R. (1985). Cancer: A world wide perspective. In: Harris, C.C. (ed). Biochemical and Molecular Epidemiology of Cancer.New York: Alan R. Liss, pp. 111–125.
7.
7. Harris, C.C. (1983). Role of carcinogens, cocarcinogens, and host factors in human cancer risk. In: Harris, C.C. (ed). Human Carcinogenesis.New York: Academic Press, pp. 941–970.
8.
8. Manchester, D.K., Weston, A., Choi, J.S., Trivers, G.E., Fennessey, P., Quintana, E., Farmer, P.B., Mann, D.L., and Harris, C.C. (1988). Detection of benzo[a]pyrene diol epoxide-DNA adducts in human placenta. Proc. Natl. Acad. Sci. USA85, 9243–9247.
9.
9. Daniel, F.B., Stoner, G.D., and Schut, H.A.J. (1983). Interindividual variation in the DNA binding of chemical genotoxins following metabolism by human bladder and bronchus explants. In:De Serres, F.J., and Pero, R. (eds). Individual Susceptibility to Genotoxic Agents in Human Population.New York: Plenum Press, pp. 177–199.
10.
10. Minchin, R.F., Mcmanus, M.E., Boobis, A.R., Davies, D.S., and Thorgeirsson, S.S. (1985). Polymorphic metabolism of the carcinogen 2-acetylaminofluorene in human liver microsomes. Carcinogenesis6, 1721–1724.
11.
11. Weston, A., Plummer, S.M., Grafstrom, R.C., Trump, B.F., and Harris, C.C. (1986). Genotoxicity of chemical and physical agents in cultured human tissues and cells. Food Chem. Toxicol.24, 675–679.
12.
12. Wogan, G.N., and Gorelick, N.J. (1985). Chemical and biochemical dosimetry of exposure to genotoxic chemicals. Environ. Health Perspect.62, 5–18.
13.
13. Lutz, W.K. (1986). Quantitative evaluation of DNA binding data for risk estimation and for classification of direct and indirect carcinogens. J. Cancer Res. Clin. Oncol.112, 85–91.
14.
14. Guengerich, P.P. (1989). Characterization of human microsomal cytochrome P-450 enzymes. Annu. Rev. Pharmacol. Toxicol.29, 241–264.
15.
15. Conney, A.H. (1982). Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G.H.A. Clowes Memorial Lecture. Cancer Res.42, 4875–4917.
16.
16. Nebert, D.W., and Negishi, M. (1982). Multiple forms of cytochrome P-450 and the importance of molecular biology and evolution. Biochem. Pharmacol.31, 2311–2317.
17.
17. Petruzzelli, S., Camus, A.M., Carrozzi, L., Ghelarducci, L., Rindi, M., Menconi, G., Angeletti, C.A., Ahotupa, M., Hietanen, E., Aitio, A., Saracci, R., Bartsch, H., and Giuntini, C. (1988). Long-lasting effects of tobacco smoking on pulmonary drug-metabolizing enzymes: A case-control study on lung cancer patients. Cancer Res.48, 4695–4700.
18.
18. Eichelbaum, M., Baur, M.P., Dengler, H.J., Osikowa-EVERS, B.O., Tieves, G., Zekoru, C., and Rittuer, C. (1987). Chromosomal assignment of human cytochrome P-450 (debrisoquine/spartein type) to chromosome 22. Cytogenet. Cell Genet.46, 610.
19.
19. Ayesh, R., Idle, J.R., Ritchie, J.C., Crothers, M.J., and Hetzel, M.R. (1984). Metabolic oxidation phenotypes as markers for susceptibility to lung cancer. Nature312, 169–170.
20.
20. Caporaso, N., Hoover, R., Eisner, S., Resau, J., Trump, B.F., Issaq, H., Morshik, G., and Harris, C.C. (1988). Debrisoquine (D) metabolic phenotype (MP) and the risk of lung cancer. FASEB J.2, C25 (abstract).
21.
21. Nowak, D., Schmidt-PREUSS, U., Jorres, R., Liebke, F., and Rudiger, H.W. (1988). Formation of DNA adducts and water-soluble metabolites of benzo[a]pyrene in human monocytes is genetically controlled. Int. J. Cancer41, 169–173.
22.
22. Poirier, M.C., Reed, E., Zwelling, L.A., Ozols, R.F., Litterst, C.L., Yuspa, S.H. (1985). Polyclonal antibodies to quantitate cis-diamminedichloroplatinum(II)—DNA adducts in cancer patients and animal models. Environ. Health Perspect.62, 89–94.
23.
23. Santella, R.M., Gasparo, F., and Hsieh, L.L. (1987). Quantitation of carcinogen-DNA adducts with monoclonal antibodies. Prog. Exp. Tumor Res.31, 63–75.
24.
24. Randerath, K., Randerath, E., Agrawal, H.P., Gupta, R.C., Schurdak, M.E., Reddy, M.V. (1985). Postlabeling methods for carcinogen-DNA adduct analysis. Environ. Health Perspect.62, 57–65.
25.
25. Rahn, R., Chang, S., Holland, J., and Shugart, L. (1982). A fluorometric-HPLC assay for quantitating the binding of benzo[a]pyrene metabolites to DNA.. Biochem. Biophys. Res. Commun.109, 262–268.
26.
26. Vahakangas, K., Haugen, A., and Harris, C.C. (1985). An applied synchronous fluorescence spectrophotometric assay to study benzo[a]pyrene-diolepoxide-DNA adducts. Carcinogenesis6, 1109–1115.
27.
27. Tornqvist, M., Osterman-GOLKAR, S., Kautiainen, A., Jensen, S., Farmer, P.B., and Ehrenberg, L. (1986). Tissue doses of ethylene oxide in cigarette smokers determined from adduct levels in hemoglobin. Carcinogenesis7, 1519–1521.
28.
28. Farmer, P.B., Bailey, E., Gorf, S.M., Tornqvist, M., Osterman-GOLKAR, S., Kautiainen, A., and Lewis-ENRIGHT, D.P. (1986). Monitoring human exposure to ethylene oxide by the determination of haemoglobin adducts using gas chromatography-mass spectrometry. Carcinogenesis7, 637–640.
29.
29. Park, J.W., Cundy, K.C., and Ames, B.N. (1989). Detection of DNA adducts by high-performance liquid chromatography with electrochemical detection. Carcinogenesis10, 827–832.
30.
30. Poirier, M.C. (1981). Antibodies to carcinogen-DNA adducts. J. Natl. Cancer Inst.67, 515–519.
31.
31. Muller, R., and Rajewsky, M.F. (1981). Antibodies specific for DNA components structurally modified by chemical carcinogens. J. Cancer Res. Clin. Oncol.102, 99–113.
32.
32. Harris, C.C., Yolken, R.H., and Hsu, I.C. (1982). Enzyme immunoassays: Applications in cancer research. In: Busch, H., and Yeoman, L.C. (eds). Methods in Cancer Research.New York: Academic Press, pp. 213–243.
33.
33. Hsu, I.C., Poirier, M.C., Yuspa, S.H., Grunberger, D., Weinstein, I.B., Yolken, R.H., Harris, C.C. (1981). Measurement of benzo(a)pyrene-DNA adducts by enzyme immunoassays and radioimmunoassay. Cancer Res.41, 1091–1095.
34.
34. Weston, A., Trivers, G.E., Vahakangas, K., Newman, M.J., Rowe, M.L., Mann, D.L., Harris, C.C. (1987). Detection of carcinogen-DNA adducts in human cells and antibodies to these adducts in human sera. In: Homburger, F., (ed.). Progress in Experimental Tumor Research.Basel: S. Karger, pp. 76–85.
35.
35. Weston, A., Newman, M.J., Vahakangas, K., Rowe, M.L., Trivers, G.E., Mann, D.L., Harris, C.C. (1987). Measurement of carcinogen-macromolecular adducts and serum antibodies recognizing DNA adducts in biological specimens from people exposed to chemical carcinogens. In: Sandhu, S.S., De Marini, D.M., Mass, M.J., Moore, M.M., and Mumford, J.L. (eds.). Short-Term Bioassays in the Analysis of Complex Environmental Mixtures V.New York: Plenum Press, pp. 91–101.
36.
36. Wilson, V.L., Basu, A.K., Essigmann, J.M., Smith, R.A., and Harris, C.C. (1988). O6-alkyldeoxyguanosine detection by 32P-postlabeling and nucleotide chromatographic analysis. Cancer Res.48, 2156–2161.
37.
37. Harris, C.C., Vahakangas, K., Newman, M.J., Trivers, G.E., Shamsuddin, A.K.M., Sinopoli, N.T., Mann, D.L., and Wright, W.E. (1985). Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers. Proc. Natl. Acad. Sci. USA82, 6672–6676.
38.
38. Hemminki, K., Perera, F.P., Phillips, D.H., Randerath, K., Reddy, M.V., Santella, R.M. (1988). Aromatic DNA adducts in white blood cells of foundry workers. In: Bartsch, H., Hemminki, K., and O'Neill, I.K. (eds.). Methods for Detecting DNA Damaging Agents in Humans: Applications in Cancer Epidemiology and Prevention.Lyon: IARC, pp. 190–195.
39.
39. Shamsuddin, A.K.M., Sinopoli, N.T., Hemminki, K., Boesch, R.R., Harris, C.C. (1985). Detection of benzo(a)pyrene: DNA adducts in human white blood cells. Cancer Res.45, 66–68.
40.
40. Poirier, M.C., Santella, R.M., Weinstein, I.B., Grunberger, D., and Yuspa, S.H. (1980). Quantitation of benzo(a)pyrene-deoxyguanosine adducts by radioimmunoassay. Cancer Res.40, 412–416.
41.
41. Foiles, P.G., Miglietta, L.M., Akerkar, S.A., Everson, R.B., and Hecht, S.S. (1988). Detection of O6-methyldeoxyguanosine in human placental DNA. Cancer Res.48, 4184–4188.
42.
42. Umbenhauer, D., Wild, C.P., Montesano, R., Saffhill, R., Boyle, J.M., Huh, N., Kirstein, U., Thomale, J., Rajewsky, M.F., and Lu, S.H. (1985). O6-methyldeoxyguanosine in oesophageal DNA among individuals at high risk of oesophageal cancer. Int. J. Cancer36, 661–665.
43.
43. Saffhill, R., Badawi, A.F., and Hall, C.N. (1988). Detection of O6-methylguanine in human DNA. In: Bartsch, H., Hemminki, K., and O'Neill, I.K. (eds.). Methods for Detecting DNA Damaging Agents in Humans: Applications in Cancer Epidemiology and Prevention.Lyon: IARC, pp. 301–305.
44.
44. Wilson, V.L., Weston, A., Manchester, D.K., Trivers, G.E., Roberts, D.W., Kadlubar, F.F., Serres, M., Wild, C.P., Montesano, R., Willey, J.C., Mann, D.L., and Harris, C.C. (1988). Alkyl and aryl carcinogen DNA adducts detected in human peripheral lung. Proc. Am. Assoc. Cancer Res.29, 261 (abstract).
45.
45. Haugen, A., Becher, G., Benestad, C., Vahakangas, K., Trivers, G.E., Newman, M.J., Harris, C.C. (1986). Determination of polycyclic aromatic hydrocarbons in the urine, benzo(a)pyrene diol epoxide-DNA adducts in lymphocyte DNA, and antibodies to the adducts in sera from coke oven workers exposed to measured amounts of polycyclic aromatic hydrocarbons in the work atmosphere. Cancer Res.46, 4178–4183.
46.
46. Autrup, H., and Wakhisi, J. (1988). Detection of exposure to aflatoxin in an african population. In: Bartsch, H., Hemminki, K., and O'Neill, I.K., (eds.). Methods for Detecting DNA Damaging Agents in Humans: Applications in Cancer Epidemiology and Prevention.Lyon: IARC, pp. 63–66.
47.
47. Sun, T., Wu, S., Wu, Y., and Chu, Y. (1988). Measurement of individual aflatoxin exposure among people having different risk to primary hepatocellular carcinoma. In: Diet, Nutrition and Cancer. Proceedings of the International Symposium of Princess Takamatsu Cancer Research Fund. in press.
48.
48. Groopman, J.D., Donahue, P.R., Zhu, J.Q., Chen, J.S., and Wogan, G.N. (1985). Aflatoxin metabolism in humans: Detection of metabolites and nucleic acid adducts in urine by affinity chromatography. Proc. Natl. Acad. Sci. USA82, 6492–6496.
49.
49. Groopman, J.D., Donahue, P.R., Zhu, J., Chen, J., and Wogan, G.N. (1987). Temporal patterns of aflatoxin metabolites in urine of people living in Guangxi Province, P.R.C. Proc. Am. Assoc. Cancer Res.28, 36–37.
50.
50. Herron, D.C., and Shank, R.C. (1980). Methylated purines in human liver DNA after probable dimethylnitrosamine poisoning. Cancer Res.40, 3116–3117.
51.
51. Dunn, B.P., and Stick, H.F. (1986). 32P-postlabelling analysis of aromatic DNA adducts in human oral mucosal cells. Carcinogenesis7, 1115–1120.
52.
52. Everson, R.B., Randerath, E., Santella, R.M., Cefalo, R.C., Avitts, T.A., Randerath, K. (1986). Detection of smoking-related covalent DNA adducts in human placenta. Science231, 54–57.
53.
53. Everson, R.B., Randerath, E., Santella, R.M., Avitts, T.A., Weinstein, I.B., Randerath, K. (1988). Quantitative associations between DNA damage in human placenta and maternal smoking and birth weight. J. Natl. Cancer Inst.80, 567–576.
54.
54. Manchester, D.K. Wilson, V.L. Weston, A. Choi, J.S. Hsu, I.C. Parker, N.B. Mann, D.L. and Harris, C.C. (1989). Polycyclic aromatic hydrocarbon-DNA adducts detected in human placenta. Carcinogenesis (in press)
55.
55. Randerath, K., Reddy, M.V., and Gupta, R.C. (1981). 32P-labeling test for DNA damage. Proc. Natl. Acad. Sci. USA78, 6126–6129.
56.
56. Gupta, R.C. (1985). Enhanced sensitivity of 32P-postlabeling analysis of aromatic carcinogen-DNA adducts. Cancer Res.45, 5656–5662.
57.
57. Dunn, B.P., and San, R.H. (1988). HPLC enrichment of hydrophobic DNA-carcinogen adducts for enhanced sensitivity of 32P-postlabeling analysis. Carcinogenesis9, 1055–1060.
58.
58. Gupta, R.C., and Earley, K. (1988). 32P-adduct assay: Comparative recoveries of structurally diverse DNA adducts in the various enhancement procedures. Carcinogenesis9, 1687–1693.
59.
59. Osterman-GOLKAR, S., Ehrenberg, L., Segerback, D., and Hallstrom, I. (1976). Evaluation of genetic risks of alkylating agents. II. Haemoglobin as a dose monitor. Mutat. Res.34, 1–10.
60.
60. Kolman, A., Naslund, M., and Calleman, C.J. (1986). Genotoxic effects of ethylene oxide and their relevance to human cancer. Carcinogenesis7, 1245–1250.
61.
61. Kelsey, K.T., Wiencke, J.K., Eisen, E.A., Lynch, D.W., Lewis, T.R., and Little, J.B. (1988). Persistently elevated sister chromatid exchanges in ethylene oxide-exposed primates: the role of a subpopulation of high frequency cells. Cancer Res.48, 5045–5050.
62.
62. Vineis, P., Esteve, J., and Terracini, B. (1984). Bladder cancer and smoking in males: Types of cigarettes, age at start, effect of stopping and interaction with occupation. Int. J. Cancer34, 165–170.
63.
63. Mommsen, S., and Aagard, J. (1983). Tobacco as a risk factor in bladder cancer. Carcinogenesis4, 335–338.
64.
64. Kadlubar, F.F., Miller, J.A., and Miller, E.C. (1977). Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis. Cancer Res.37, 805–814.
65.
65. Bryant, M.S., Vineis, P., Skipper, P.L., Tannenbaum, S.R. (1988). Haemoglobin adducts of aromatic amines in people exposed to cigarette smoke. In: Bartsch, H., Hemminki, K., and O'Neill, I.K. (eds). Methods for Detecting DNA Damaging Agents in Humans: Applications in Cancer Epidemiology and Prevention.Lyon: IARC, pp. 133–136.
66.
66. Bryant, M.S., Skipper, P.L., Tannenbaum, S.R., and Maclure, M. (1987). Hemoglobin adducts of 4-aminobiphenyl in smokers and nonsmokers. Cancer Res.47, 602–608.
67.
67. Wild, C.P., Chapot, B., Scherer, E., Den Engelse, L., and Montesano, R. (1988). Application of antibody methods to the detection of aflatoxin in human body fluids. In: Bartsch, H., Hemminki K., and O'Neill, I.K. (eds.). Methods for Detecting DNA Damaging Agents in Humans: Applications in Cancer Epidemiology and Prevention.Lyon: IARC, pp. 67–74.
68.
68. Tannenbaum, S.R., and Skipper, P.L. (1984). Biological aspects to the evaluation of risk: dosimetry of carcinogens in man. Fund. Appl. Toxicol.4, S367–S373.
69.
69. Newman, M.J., Light, B.A., Weston, A., Tollurud, D., Clark, J.L., Mann, D.L., Blackmon, J.P., Harris, C.C. (1988). Detection and characterization of human serum antibodies to polycyclic aromatic hydrocarbon diol-epoxide DNA adducts. J. Clin. Invest.82, 145–153.
70.
70. Brooks, B., Bruccoleri, R., Olarson, B., States, D., Swiminathan, S., and Karplus, M. (1983). CHARRM: A program for molecular energy minimization, and dynamics calculations. J. Comp. Chem.4, 187–196.
71.
71. Haverkorn, M.J., Hofman, B., Masurel, N., and Van Rood, J.J. (1975). HL-A linked genetic control of immune responses in man. In: Moller, G. (ed.). Transplantation Reviews.Copenhagen: Munksgaard, pp. 120–124.
72.
72. Osoba, D., Dick, H.M., Voller, A., Goosen, T.J., Goosen, T., Draper, C.C., and De The, G. (1979). Role of the HLA complex in the antibody response to malaria under natural conditions. Immunogenetics8, 323–338.
73.
73. Mann, D.L., Mendell, N., Kahn, C.R., Johnson, A.H., Rosenthal, A. (1983). In vitro lymphocyte proliferation response to therapeutic insulin components. Evidence for genetic control by the human major histocompatibility complex. J. Clin. Invest.72, 1130–1138.
74.
74. Schwartz, R.L. (1986). Immune response genes of the murine major histocompatibility complex. Adv. Immunol.38, 31–201.
75.
75. Giles, R.E., and Capra, J.D. (1985). Structure, function and genetics of human class II molecules. Adv. Immunol.27, 1–73.
76.
76. Kuchino, Y., Mori, F., Kasai, H., Inoue, H., Iwai, S., Miura, K., Ohtsuka, E., and Nishimura, S. (1987). Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues. Nature327, 77–79.
77.
77. Wallace, S.S. (1987). The biological consequences of oxidized DNA bases. Br. J. Cancer [Suppl.]8, 118–128.
78.
78. Teebor, G.W., Boorstein, R.J., and Cadet, J. (1988). The repairability of oxidative free radical mediated damage to DNA: A review. Int. J. Radiat. Biol.54, 131–150.
79.
79. Mereghini, R. (1988). Genotoxicity of active oxygen species in mammalian cells. Mutat. Res.195, 215–230.
80.
80. Leadon, S.A., Stampfer, M.R., and Bartley, J. (1988). Production of oxidative DNA damage during the metabolic activation of benzo[a]pyrene in human mammary epithelial cells correlates with cell killing. Proc. Natl. Acad. Sci. U.S.A.85, 4365–4368.
81.
81. Lesko, S.A., Trpis, L., and Zheng, R. (1986). Somatic mutation, DNA damage and cytotoxicity induced by benzo[a]pyrenedione/benzo[a]pyrenediol redox couples in cultured mammalian cells. Mutat. Res.161, 173–180.
82.
82. Kaneko, M., and Leadon, S.A. (1986). Production of thymine glycols in DNA by N-hydroxy-2-naphthylamine as detected by a monoclonal antibody. Cancer Res.46, 71–75.
83.
83. Lewis, J.G., Stewart, W., and Adams, D.O. (1988). Role of oxygen radicals in induction of DNA damage by metabolites of benzene. Cancer Res.48, 4762–4765.
84.
84. Halliwell, B. (1987). Oxidants and human disease: Some new concepts. FASEB J.1, 358–364.
85.
85. Gabrielson, E.W., and Harris, C.C. (1985). Use of cultured human tissues and cells in carcinogenesis research. J. Cancer Res. Clin. Oncol.110, 1–10.
86.
86. West, G.J., West, I.W., and Ward, J.F. (1982). Radioimmunoassay of 7,8-dihydro-8-oxoadenine (8-hydroxyadenine). Int. J. Radiat. Biol.42, 481–490.
87.
87. Leadon, S.A. (1987). Production of thymine glycols in DNA by radiation and chemical carcinogens as detected by a monoclonal antibody. Br. J. Cancer [Suppl.]8, 113–117.
88.
88. Cathcart, R., Schwiers, E., Saul, R.L., Ames, B.N. (1984). Thymine glycol and thymidine glycol in human and rat urine: A possible assay for oxidative DNA damage. Proc. Natl. Acad. Sci. USA81, 5633–5637.
89.
89. Frenkel, K., Cummings, A., Solomon, J., Cadet, J., Steinberg, J.J., Teebor, G.W. (1985). Quantitative determination of the 5-(hydroxymethyl)uracil moiety in the DNA of gamma-irradiated cells. Biochemistry24, 4527–4533.
90.
90. Frenkel, K., Goldstein, M.S., and Teebor, G.W. (1981). Identification of the cis-thymine glycol moiety in chemically oxidized and gamma-irradiated deoxyribonucleic acid by high-pressure liquid chromatography analysis. Biochemistry20, 7566–7571.
91.
91. Floyd, R.A., Watson, J.J., Wong, P.K., Altimiller, D.H., and Rickard, R.C. (1986). Hydroxyl free radical adduct of deoxyguanosine: Sensitive detection and mechanisms of formation. Free Radical Res. Commun.1, 163–172.
92.
92. Dizdaroglu, M., and Bergtold, D.S. (1986). Characterization of free radical-induced base damage in DNA at biologically relevant levels. Anal. Biochem.156, 182–188.
93.
93. Leadon, S.A., and Hanawalt, P.C. (1983). Monoclonal antibody to DNA containing thymine glycol. Mutat. Res.112, 191–200.
94.
94. Saul, R.L., and Ames, B.N. (1986). Background levels of DNA damage in the population. In: Simic, M.G., Grossman, L., and Upton, A.C. (eds.). Mechanisms of DNA Damage and Repair: Implications for Carcinogenesis and Risk Assessment.New York: Plenum Press, pp. 529–535.
95.
95. Richter, C., Park, J.W., and Ames, B.N. (1988). Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc. Natl. Acad. Sci. U.S.A.85, 6465–6467.
96.
96. Hanawalt, P.C. (1987). Preferential DNA repair in expressed genes. Environ. Health Perspect.76, 9–14.
97.
97. Kasai, H., Nishimura, S., Kurokawa, Y., and Hayashi, Y. (1987). Oral administration of the renal carcinogen, potassium bromate, specifically produces 8-hydroxydeoxyguanosine in rat target organ DNA. Carcinogenesis8, 1959–1961.
98.
98. Hashimoto, Y., and Shudo, K. (1985). Chemical modification of DNA with muta-carcinogens. I 3-Amino-1-methyl-5H-pyrido[4,3-b]indole and 2-amino-6-methyldipyrido[1,2-a:3′,2′-d]imidazole: Metabolic activation and structure of the DNA adducts. Environ. Health Perspect.62, 209–214.
99.
99. Kohda, K., Tada, M., Kasai, H., Nishimura, S., and Kawazoe, Y. (1986). Formation of 8-hydroxyguanine residues in cellular DNA exposed to the carcinogen 4-nitroquinoline 1-oxide. Biochem. Biophys. Res. Commun.139, 626–632.
100.
100. Loeb, L.A., and Preston, B.D. (1986). Mutagenesis by apurinic/apyrimidinic sites. Annu. Rev. Genet.20, 201–230.
101.
101. Loeb, L.A., James, E.A., Waltersdorph, A.M., and Klebanoff, S.J. (1988). Mutagenesis by the autoxidation of iron with isolated DNA. Proc. Natl. Acad. Sci. U.S.A.85, 3918–3922.
102.
102. Vahakangas, K., Pelkonen, O., and Harris, C.C. (1988). Synchronous fluorescence spectrophotometry of benzo[a]pyrene diol epoxide-DNA adducts: A tool for detection of in-vitro and in-vivo DNA damage by exposure to benzo[a]pyrene. In: Bartsch, H., Hemminki, K., and O'Neill, I.K. (eds.). Methods for Detecting DNA Damaging Agents in Humans: Applications in Cancer Epidemiology and Prevention.Lyon: IARC, pp. 208–212.
103.
103. Phillips, D.H., Hewer, A.J., and Grover, P.L. (1986). Aromatic DNA adducts in human bone marrow and peripheral blood leukocytes. Carcinogenesis7, 2071–2075.
104.
104. Randerath, E., Avitts, T.A., Reddy, M.V., Miller, R.H., Everson, R.B., and Randerath, K. (1986). Comparative 32P-analysis of cigarette smoke-induced DNA damage in human tissues and mouse skin. Cancer Res.46, 5869–5877.
