Xenobiotic studies in laboratory animals and tissues and cells in vitro have shown that the formation of carcinogen-DNA adducts is central to theories of chemical carcinogenesis. It seems reasonable to attempt to seek evidence of these types of adducts in humans following environmental exposure. The biologically effective dose of a chemical carcinogen is governed by the amount of carcinogen that reaches a target tissue or surrogate in a form that becomes activated in that tissue to a chemical species capable of causing lesions in DNA. Human carcinogen dosimetry at the molecular level requires sensitive and specific methods for carcinogen-macromolecular adduct quantitation. The low levels of adducts present in human DNA samples challenge the detection limits of conventional assay systems and complex mixtures of adducted materials confound simple assay systems. A number of different types of methods have been developed for carcinogen-DNA dosimetry in humans. Specifically, the most commonly used methods for human carcinogen-DNA adduct measurement are 32P-nucleotide postlabeling, immunoassays, fluorescence spectroscopy, electrochemical conductance and gas chromatography/mass spectroscopy (GC/MS). Each of these techniques currently has its own advantages and limitations, and within the framework of epidemiological surveys multiple corroborative end-point analyses often provide the most useful information. Our studies have focused on the use of separatory techniques in order to achieve chemical specificity prior to sensitive detection by multiple corroborative end-points.
