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.
Wood preserving waste (WPW) sites contain numerous toxic compounds, including phenols, polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzodioxins, and dibenzofurans. Previous in vitro and in vivo 32P-postlabeling studies showed the induction of multiple carcinogen-DNA adducts by WPW extracts. We now have tested the hypothesis in a mouse skin bioassay that a WPW extract not only causes the formation of exogenous, xenobiotic-derived DNA adducts, but also alters the levels of endogenous DNA modifications. Skin DNA of female ICR mice treated topically with an organic WPW extract was found by 32P-postlabeling to contain significantly increased levels of bulky oxidative DNA lesions (type II I-compounds), in addition to exogenous PAH-derived adducts. The mechanism of this increase is postulated to proceed through electrophilic quinoid compounds, which presumably were formed from phenols by chemical reactions of waste material or biologically by oxidative metabolism. On the other hand, the levels of another class of endogenous DNA adducts (type I I-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 endogenous DNA modifications may need to be considered in evaluating carcinogenic risk from toxic chemical wastes and the effects of remediation measures.
Randerath
K
K
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA.
Zhou
G D
GD
Randerath
E
E
Safe
S H
SH
Donnelly
K C
KC
D000096:Acetone / Q000633:toxicity; D000818:Animals; D018736:DNA Adducts / Q000032:analysis* / Q000378:metabolism; D005260:Female; D005609:Free Radicals; D007553:Isotope Labeling / Q000379:methods*; D051379:Mice; D008813:Mice, Inbred ICR; D010416:Pentachlorophenol / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D010761:Phosphorus Radioisotopes; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000633:toxicity; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D012867:Skin / Q000187:drug effects*; D014866:Waste Products / Q000009:adverse effects* / Q000032:analysis; D014934:Wood
D018736:DNA Adducts; D005609:Free Radicals; D010761:Phosphorus Radioisotopes; D011084:Polycyclic Aromatic Hydrocarbons; D014866:Waste Products; D000096:Acetone; D010416:Pentachlorophenol; D015719:Single-Strand Specific DNA and RNA Endonucleases