The development, application and validation of biomarkers for carcinogen exposure are directed at carcinogen exposures leading to the biologically effective dose. Chemically specific and quantitatively reliable assays have been developed for the detection of polycyclic aromatic hydrocarbon- DNA adducts, 7-methyl-dGp adducts and 7-ethyl-dGp adducts using immunoaffinity chromatography, high performance liquid chromatography and the 32P-postlabeling assay. The assays have been or are being corroborated by alternate detection systems. The assays were applied to a sample set of 91 human lungs from an autopsy donor program. 7-alkyl-dGp adducts were highly correlated with each other but not with PAH-adducts, suggesting that inheritable susceptibilities mediate adduct levels whereby the alkyl adducts are correlated because they share similar pathways. PAH-DNA adducts are not correlated because they are activated by different pathways. The presence of PAH-DNA adducts were highly associated with the null glutathione-S-transferase genotype, indicating the strong determinant of adduct formation by this detoxification enzyme. It also was found that 7-methyl-dGp was correlated with the CYP2E1 genotype. Separately, the detection of benzo[a]pyrene metabolites in human urine using immunoaffinity chromatography, high performance liquid chromatography and synchronus fluorescence detection was increased in persons treated with coal tar for skin diseases. The methodology also detected 1-OH-pyrene, which also correlates with exposure. In a study of foundry workers, serum anti-PAH-DNA antibodies was found to correlate with exposure, suggesting that antibody detection with ELISA might be a reliable exposure biomarker, which is also less expensive than adduct detection methods.
