DNA adduct determination in humans

Carcinogen-DNA adduct formation, presumed to constitute tumorigenic initiation, provides irrefutable evidence of exposure and some indication of biologically effective dose to target tissues. Carcinogen-DNA adducts, representing a broad spectrum of chemical and physical insult, have been measured in humans using a variety of recently-developed, highly sensitive techniques. Evaluation of the results of these assays relies on detailed understanding of the strengths and weaknesses of the assays themselves. This review is primarily focussed on the application of immunoassays and 32P-postlabeling for human DNA adduct monitoring. Purification of adducts by high performance liquid chromatography or immunoaffinity chromatography, and structural determination by chemically-specific procedures such as synchronous fluorescence spectrometry and gas chromatography/mass spectrometry are also described. In addition, studies in which human DNA adduct dosimetry has been achieved are presented and evaluated.