DNA adducts, mutations, and cancer 2000

The main achievements in the DNA adduct field in the 1990s have been techni cal innovations of methods for specific adducts reaching sensitivities requ ired for low levels encountered in humans. Over 20 specific adducts or clos ely related groups of adducts have been determined in humans. The sources o f the DNA-binding agents are endogenous and exogenous or both. in some of t hese studies adduct levels have been correlated to metabolic or DNA repair genotypes. An example of DNA adduct studies in human target tissue is taken on UV photoproducts in skin in situ. Adduct-induced mutations, specific mu tation spectra, and their relationship to cancer are discussed, The quantit ative adduct techniques will enable comparisons of endogenous and exogenous adduct levels and will give important clues to the etiology of human cance r. Furthermore, adducts will provide an intermediary tool for genotyping st udies, both for metabolic enzyme and for DNA repair system genotypes. As th e common polymorphisms are likely to cause at most moderate increases in th e risk of cancer, the intermediary adduct endpoint is a necessary proof of causal relationships. The present and future biomonitoring studies will cov er many endpoints to link the mechanistic steps from DNA adducts to cancer via mutations and modulating host susceptibility factors. (C) 2000 Academic Press.