OXIDATIVE DNA-DAMAGE - THE EFFECTS OF CERTAIN GENOTOXIC AND OPERATIONALLY NONGENOTOXIC CARCINOGENS

A wide variety of oxidative DNA lesions are commonly present in untrea ted human and animal DNA. One of these lesions, 8-hydroxydeoxyguanosin e, has been shown to lead to base mispairing (mutation) on DNA replica tion. Other lesions remain to be investigated in this respect. Oxidati ve DNA lesions on cell replication may, in appropriate circumstances, lead to proto-oncogene activation. Oxidative DNA damage, on fixation, may also lead to cytotoxicity followed by regenerative proliferation. The probable or possible importance of oxidative DNA damage is reviewe d for various classes of carcinogens and natural processes, including metal ions, high-energy radiation, miscellaneous chemicals, tumor-prom oting agents, polyhydroxyphenols/quinones, lipid metabolism peroxisome proliferators and thyroid function. It is concluded that although the evidence needs considerable strengthening in many of these examples, the available information indicates the potential importance of oxidat ive DNA damage in the induction of tumors by these agents. It is also possible that non-cancerous degenerative diseases associated with agin g are the result of the accumulation of lesions resulting from unrepai red oxidative DNA damage.