Studies using specific biomarkers for human exposure assessment to exogenous and endogenous chemical agents

The extent of formation of carcinogen adducts with DNA and protein may be u sed to assess the biologically effective dose of these carcinogens in the t issue under study. In normal human tissues, such carcinogen adducts arise i n part from exposures to exogenous genotoxic compounds, although it has bee n shown that endogenously formed carcinogens also make a significant contri bution to the observed DNA and protein damage. Although, highly sensitive a nalytical methods, such as immunoassay, P-32-postlabelling and mass spectro metry have been developed and successfully applied to measure carcinogen ad ducts, further methodological advances are making these methods more amenab le to molecular epidemiological studies. Thus, the use of immunoslot blot a ssays allows a higher sample throughput for adduct quantification. Liquid c hromatographic separations of adducts, either for their radiochemical detec tion following P-32-postlabelling or for their determination by mass spectr ometry, improves the specificity and applicability of these techniques. In this review, the sensitivities and specificities of the analytical methods used for adduct detection are compared and the limitations of these methods described. (C) 1999 Elsevier Science B.V. All rights reserved.