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Pentachlorophenol potentiates benzo[a]pyrene DNA adduct formation in adult but not infant B6C3F1 male mice †
Author(s) -
Bordelon Nancy R.,
Donnelly Kirby C.,
George S. Elizabeth
Publication year - 2001
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.1024
Subject(s) - pentachlorophenol , deoxyguanosine , chemistry , benzo(a)pyrene , pyrene , carcinogen , dna adduct , adduct , genotoxicity , ratón , dna , microbiology and biotechnology , toxicity , endocrinology , biochemistry , medicine , biology , organic chemistry , environmental chemistry
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 μg B[a]P/g body weight (BW) alone and in combination with several doses of PCP in DMSO. The 32 P‐postlabeling assay was used to analyze for (±) anti‐ 7,8‐diol‐9,10‐epoxide‐B[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‐N 2 G accumulation in infant mice exposed to B[a]P in combination with 50 μg PCP/g BW at both 12 and 24 hr. Comparatively, BPDE‐N 2 G 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. Environ. Mol. Mutagen. 37:164–172, 2001 Published 2001 Wiley‐Liss, Inc.