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Abstract
Formation of PAH-DNA base adducts is an accepted tumor-initiating event. However, it is not yet known what constitutes tumor promotional processes engendered by complete carcinogens. It appears that induction of oxidative stress and oxidative DNA damage optimally correlates with the biological effects of tumor promoters. We showed that PAH-treated rat liver microsomes produce superoxide (O2·-) and hydrogen peroxide (H2O2) that cause oxidation of bases in DNA. Recently we found that 7,12-dimethylbenz[a]anthracene (DMBA) induces in vivo some of the same responses as those mediated by phorbol ester tumor promoters. These include inflammatory processes, H2O2 production and oxidation of bases in the epidermal DNA of topically-treated SENCAR mice. Those responses occurred in long (5 wk)- and short (4 day)-term DMBA treatments. Based on these findings, we propose that PAH-induced inflammation, generation of oxidants and oxidation of bases in DNA represent tumor promotional processes of complete carcinogenesis.