Pentachlorophenol potentiates benzo[a]pyrene DNA adduct formation in adult but not infant B6C3F1 male mice

The objective of this study is to determine whether pentachlorophenol (PCP) alters benzo[a]pyrene (B[a]P)-induced DNA adduct Formation in infant and adult B6C3F1 male mice. Mice were exposed intraperitoneally to 55 mug B[a]P/g body weight (BW) alone and in combination with several doses of PCP in DMSO. The P-32-postlabeling assay was used to analyze For (+/-) anti-7,8diol-9,10-epoxideB[a] P-N(2)deoxyguanosine (BPDE-N(2)G) adducts formed in liver and lung DNA. Hepatic DNA also was analyzed For 8-hydroxy-2 ' -deoxyguanosine (8-OHdG) base damage in mice exposed to PCP. 8-OHdG was not detected at any dose of PCP in infant or adult mice. PCP exhibited an antagonistic effect on BPDE-N2G accumulation in infant mice exposed to B[a]P in combination with 50 mug PCP/g BW at both 12 and 24 hr. Comparatively, BPDE-N2G adducts were increased in adult mice exposed to binary mixtures at 24 hr in both hepatic and lung DNA (P < 0.05). Multiple comparison analysis between infant and adult mice revealed that adduct levels in infants exposed to B[a]P alone or in combination with PCP were not different from those observed in adult mice exposed to B[a]P. However, a significant increase in adducts was observed in adult mice exposed to a combination of B[a]P and PCP compared to that in all other treatment groups (P < 0.05). These results suggest that PCP alters the metabolism of B[a]P in both infant and adult mice through different mechanisms, and that infants are not susceptible to the potentiating effects of PCP observed in adult mice. Published 2001 Wiley-Liss, Inc.(dagger).