DNA adducts: Endogenous and induced

Human exposure to DNA damaging agents can arise from exogenous sources or e ndogenous processes that occur normally or in pathological states. DNA isol ated from human tissues, obtained from the very young to the old, contains detectable amounts of a number of different types of DNA adducts that refle ct exposure to both known carcinogens and as yet unidentified genotoxic age nts. The levels of DNA damage observed in human studies as a result of exog enous exposures (noniatrogenic) is of the order of 1 adduct per 10(7)-10(9) normal DNA bases, whereas that arising from endogenous exposures may poten tially be several orders of magnitude higher. Large interindividual variati ons in DNA adduct levels have been reported, and these are probably the res ult of host and environmental factors, although variation in analytical and sampling procedures may also play a role. It is important to recognize tha t the presence of DNA adducts in a tissue does not necessarily indicate a s pecific tumorigenic risk for that tissue, as other factors downstream of DN A adduct formation (including DNA repair and cell proliferation) play an im portant role in determining overall risk.