Markers of Exposure to Carcinogens: Methods for Human Biomonitoring

Abstract

Methods have been developed for the detection of exposure to carcinogens and other DNA-damaging agents in experimental animals and humans, through the detection of carcinogens or metabolic derivatives of them in body fluids or adducts bound covalently to DNA or hemoglobin. These methods are being applied in studies of exposure to environmental carcinogens, the results of which demonstrate their adequacy for detecting ambient exposures. The successful use of urinary markers of genotoxic exposures has been reported with respect to nitrosoproline as an indicator of exposure to N-nitroso compounds. The same approach has been used to detect aflatoxin B1 (AFB1) metabolites and AFB1-N7-Gua as markers of exposure to aflatoxin B1. 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-hydroxyva-line 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. Albumin adducts of AFB1 have been identified in exposed people and their levels correlated with ingested amounts of the carcinogen. DNA adducts of genotoxic agents have also been detected in the cells and tissues of exposed individuals. Several studies to date have focused on exposure to the ubiquitous polycyclic aromatic hydrocarbon benzo(a)pyrene. Immunoassays and physicochemical methods have been used to detect adducts formed through the major intermediate in the activation pathway, the benzpyrene-7,8-diol-9,10-epoxide (BPDE). BPDE adducts have been found in the DNA of peripheral leukocytes of workers in foundries, aluminum manufacturing plants, and coke oven plants, and also in roofers and cigarette smokers with the use of synchronous scanning fluorescence as well as by enzyme-linked immunosorbent assays (ELISA) or ultrasensitive enzyme radioimmunoassays (USERIA). DNA adducts of O6-methyl guanine have also been detected by immunoassay in the blood of populations at high risk for esophageal cancer. The method of 32P postlabeling has been used for the detection of DNA adducts in placentas, peripheral leukocytes, and oral mucosal cells of tobacco smokers as well as coke oven and foundry workers, and increased total levels of adducts were in general indicative of elevated levels of exposure.