The concept that the formation of carcinogen-DNA adducts is necessary but not sufficient for carcinogenesis by certain chemicals has been indicated by experiments in laboratory animals. Following environmental exposure, it is known that adducts are formed in humans because the biologically effective dose of a chemical carcinogen is governed by the amount of carcinogen that becomes internalized and activated to a chemical species capable of damaging DNA. Thus, we seek to develop methods to detect these adducts. Human carcinogen dosimetry at the molecular level requires sensitive and specific methods for carcinogen-macromolecular adduct quantitation. A number of different types of methods have been developed for dosimetry in humans. These include the 32P-postlabeling assay, enzyme-immunoassays, fluorescence spectroscopy, electrochemical conductance and gas chromatography/mass spectroscopy. Each technique has advantages and limitations; and within the framework of epidemiological surveys, multiple corroborative end-point analyses often provide the most useful information. Current studies are focused upon the use of separatory techniques to achieve chemical specificity prior to sensitive detection by different corroborative methods. In addition to seeking evidence of covalent binding of activated PAH to DNA, a method has also been developed to measure tetrahydrotetrol levels of benzo[`]pyrene in human urine.
