COMPARATIVE P-32 POSTLABELING ANALYSIS OF EXOGENOUS AND ENDOGENOUS DNA-ADDUCTS IN MOUSE SKIN EXPOSED TO A WOOD-PRESERVING WASTE EXTRACT, A COMPLEX MIXTURE OF POLYCYCLIC AND POLYCHLORINATED CHEMICALS

Wood preserving waste (WPW) sites contain numerous toxic compounds, in cluding phenols, polycyclic aromatic hydrocarbons (PAHs), polychlorina ted dibenzodioxins, and dibenzofurans. Previous in vitro and in vivo P -32-postlabeling studies showed the induction of multiple carcinogen-D NA adducts by WPW extracts. We now have tested the hypothesis in a mou se skin bioassay that a WPW extract not only causes the formation of e xogenous, xenobiotic-derived DNA adducts, but also alters the levels o f endogenous DNA modifications. Skin DNA of female ICR mice treated to pically with an organic WPW extract was found by P-32-postlabeling to contain significantly increased levels of bulky oxidative DNA lesions (type II I-compounds), in addition to exogenous PAH-derived adducts. T he mechanism of this increase is postulated to proceed through electro philic quinoid compounds, which presumably were Formed from phenols by chemical reactions of waste material or biologically by oxidative met abolism. On the other hand, the levels of another class of endogenous DNA adducts (type II-compounds) were reduced significantly in exposed skin DNA. This effect was explained by the presence of cytochrome P450 inducers in the extract. All three types of DNA alterations observed may play a significant role in carcinogenesis. Our results imply that in addition to exogenous carcinogen-DNA adducts, alterations of endoge nous DNA modifications may need to be considered in evaluating carcino genic risk from toxic chemical wastes and the effects of remediation m easures. (C) 1997 Wiley-Liss, Inc.