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 microg B[a]P/g body weight (BW) alone and in combination with several doses of PCP in DMSO. The 32P-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 microg 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.
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station, Texas, USA. Bordelo1@niehs.nih.gov
N R
NR
Bordelon
K C
KC
Donnelly
S E
SE
George
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001564:Benzo(a)pyrene / Q000633:toxicity*; D018736:DNA Adducts / Q000096:biosynthesis*; D004357:Drug Synergism; D008297:Male; D051379:Mice; D010416:Pentachlorophenol / Q000633:toxicity*
D018736:DNA Adducts; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D010416:Pentachlorophenol