Comparative 32P-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
✍ Scribed by K. Randerath; G.-D. Zhou; E. Randerath; S.H. Safe; K.C. Donnelly
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 154 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0893-6692
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✦ Synopsis
Wood preserving waste (WPW) sites contain nu-electrophilic quinoid compounds, which presummerous toxic compounds, including phenols, poly-ably were formed from phenols by chemical reaccyclic aromatic hydrocarbons (PAHs), polychlori-tions of waste material or biologically by oxidative nated dibenzodioxins, and dibenzofurans. Previous metabolism. On the other hand, the levels of anin vitro and in vivo 32 P-postlabeling studies showed other class of endogenous DNA adducts (type I Ithe induction of multiple carcinogen-DNA adducts compounds) were reduced significantly in exposed by WPW extracts. We now have tested the hypoth-skin DNA. This effect was explained by the presesis in a mouse skin bioassay that a WPW extract ence of cytochrome P450 inducers in the extract. not only causes the formation of exogenous, xenobi-All three types of DNA alterations observed may otic-derived DNA adducts, but also alters the levels play a significant role in carcinogenesis. Our results of endogenous DNA modifications. Skin DNA of imply that in addition to exogenous carcinogenfemale ICR mice treated topically with an organic DNA adducts, alterations of endogenous DNA WPW extract was found by 32 P-postlabeling to con-modifications may need to be considered in evaluattain significantly increased levels of bulky oxidative ing carcinogenic risk from toxic chemical wastes DNA lesions (type II I-compounds), in addition to and the effects of remediation measures. Environ. exogenous PAH-derived adducts. The mechanism Mol. Mutagen. 29:372 -378, 1997 of this increase is postulated to proceed through ᭧ 1997 Wiley-Liss, Inc.