Markers of Exposure to Carcinogens
Environmental Health Perspectives
Methods have been developed for the detection of exposure to carcinogens and other DNA damaging agents in experimental animals and man through the detection of carcinogens or their metabolic derivatives in body fluids, or through adducts bound covalently to DNA or hemoglobin. The successful use of urinary markers of genotoxic exposures has been reported with respect to nitrosoproline as an indicator of exposure to Nnitroso compounds. The same approach has been used to detect AFBI and
... AFBI and AFB1-N7-Gua as markers of exposure to aflatoxin B,; of 3-methyladenine produced as a result of exposure to methylating agents; and thymine glycol as an indicator of exposure to agents causing oxidative damage to DNA. Detection of adducts formed between genotoxic agents and hemoglobin has been reported in studies of populations occupationally exposed to ethylene oxide, in which 3-hydroxyhistidine and 3-hydroxyvaline have been measured, and in smokers, whose hemoglobin has been found to contain levels of 4-aminobiphenyl and 3-hydroxyvaline that were correlated with the frequency of cigarette smoking. Detection of DNA adducts of genotoxic agents in the cells and tissues of exposed individuals has also been accomplished through the use of several types of analytical methods. Immunoassays and physicochemical methods have been applied to detect adducts formed through the major intermediate in the activation of benzo(a)pyrene, the 7,8-diol-9,10-epoxide (BPDE). This adduct has been found in the DNA of peripheral leukocytes of workers in foundries, aluminum manufacturing plants, roofers, and coke oven plants, and also in cigarette smokers. BPDE-DNA adducts have been detected by synchronous scanning fluorescence as well as by immunoassays conducted in ELISA or USERIA modes. The successful application of immunoassays to detect DNA adducts of cis-platinum in leukocytes of ovarian cancer patients receiving chemotherapy and 06-methyl guanine in the blood of populations at high risk for esophageal cancer has also been reported. The method of 32P-postlabeling for the detection of DNA adducts has confirmed their presence in placentas, peripheral leukocytes, and oral mucosal cells of tobacco smokers, as well as coke oven and foundry workers. Increased total levels of adducts were, in general, reflective of elevated levels of exposure.