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THE EFFECT OF PENTACHLOROPHENOL ON DNA ADDUCT FORMATION IN C57B1/6 TRP53 +/+ AND C57B16 TRP53 -/- MICE EXPOSED TO BENZO[A]PYRENE MAY BE ASSOCIATED WITH P53 FUNCTION.
Citation:
Bordelon, N., K. C. Donnelly, AND S E. George. THE EFFECT OF PENTACHLOROPHENOL ON DNA ADDUCT FORMATION IN C57B1/6 TRP53 +/+ AND C57B16 TRP53 -/- MICE EXPOSED TO BENZO[A]PYRENE MAY BE ASSOCIATED WITH P53 FUNCTION. CANCER LETTERS 178(1):11-17, (2000).
Description:
Abstract
Previous studies have shown that pentachlorophenol (PCP) has both potentiative and antagonistic effects on the genotoxicity of benzo[a]pyrene (B[a]P). It has been suggested that these effects are due to inhibition and/or induction of enzymes involved in the biotransformation of B[a]P (Moorthy and Randerath, 1996). However, B[a]P (Pei et al., 1999) and a metabolite of PCP, tetrachlorohydroquinone (C14-TCHQ) (Wang et al., 1997), induce p53 protein in vitro. To investigate this effect further, C57BL6Tac trp53+1+ (WT) and C57BL6Tac trp53-1- (KO) mice were exposed to 55 ug B[a]P/g BW alone and in combination with 25 ug/g PCP. Hepatic and lung DNA were analyzed for the major B[a]P DNA adduct, 7R, 8S, 9S-trihydroxy-1OR-(N2-2'-deoxygaunosyl)7,8,9,10-tetrahydro-B[a]P (BPDE-N2G) and other minor adducts using the 32p- postlabeling assay. BPDE-N2G adducts were detected in all treatment groups. Similar adduct levels were observed in WT mice exposed to 55 ug/g B[a]P compared to knockout mice exposed to B[a]P alone and in combination with PCP. Interestingly, PCP inhibited BPDE-N2G adduct formation in p53 WT mice exposed to B[a]P in a mixture with PCP in both hepatic and lung DNA (p < 0.05). PCP also inhibited total DNA adduct levels in hepatic DNA (p < 0.05) but had no effect on lung DNA adducts in WT mice. PCP did not effect total DNA adduct levels in either hepatic or lung DNA isolated from KO mice. These results suggest that the decrease in BPDE-N2 G adducts observed in KO mice may be a result of p53 accumulation and induction of repair pathways in response to damage induced by PCP.
This abstract does not necessarily reflect US EPA policy.