PMID- 16094661 OWN - NLM STAT- MEDLINE DCOM- 20060421 LR - 20151123 IS - 0893-6692 (Print) IS - 0893-6692 (Linking) VI - 47 IP - 1 DP - 2006 Jan TI - 3,4-Epoxy-1-butene, a reactive metabolite of 1,3-butadiene, induces somatic mutations in Xpc-null mice. PG - 67-70 AB - Xpc-null (Xpc-/-) mice, deficient in the global genome repair subpathway of nucleotide excision repair (NER-GGR), were exposed by intraperitoneal (i.p.) injection to a 300 mg/kg mutagenic dose of 3,4-epoxy-1-butene (EB), to investigate NER's potential role in repairing butadiene (BD) epoxide DNA lesions. Mutagenic sensitivity was assessed using the Hprt assay. Xpc-/- mice were significantly more sensitive to EB exposure, exhibiting an average 2.8-fold increase in Hprt mutant frequency (MF) relative to those of exposed Xpc+/+ (wild-type) mice. As a positive control for NER-GGR, additional mice were exposed by i.p. injection to a 150 mg/kg mutagenic dose of benzo[a]pyrene (B[a]P). The Xpc-/- mice had MFs 2.9-fold higher than those of exposed Xpc+/+ mice. These results suggest that NER-GGR plays a role in recognizing and repairing some of the DNA adducts formed following in vivo exposure to EB. Additional research is needed to examine the response of Xpc-/- mice, as well as other NER-deficient strains, to inhaled BD. Furthermore, it is likely that alternative DNA repair pathways also are involved in restoring genomic integrity compromised by BD-epoxide DNA damage. Collaborative studies are currently underway to address these critical issues. CI - 2005 Wiley-Liss, Inc. FAU - Wickliffe, J K AU - Wickliffe JK AD - Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas, USA. jkwickli@utmb.edu FAU - Galbert, L A AU - Galbert LA FAU - Ammenheuser, M M AU - Ammenheuser MM FAU - Herring, S M AU - Herring SM FAU - Xie, J AU - Xie J FAU - Masters, O E 3rd AU - Masters OE 3rd FAU - Friedberg, E C AU - Friedberg EC FAU - Lloyd, R S AU - Lloyd RS FAU - Ward, J B Jr AU - Ward JB Jr LA - eng GR - 1 P30-ES06676/ES/NIEHS NIH HHS/United States GR - 2R01ES06015-07/ES/NIEHS NIH HHS/United States GR - S11 ES-10018/ES/NIEHS NIH HHS/United States GR - T32-ES07254/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Environ Mol Mutagen JT - Environmental and molecular mutagenesis JID - 8800109 RN - 0 (DNA Adducts) RN - 0 (DNA-Binding Proteins) RN - 0 (Epoxy Compounds) RN - 0 (Mutagens) RN - 0 (Xpc protein, mouse) RN - 3417WMA06D (Benzo(a)pyrene) RN - 478ERR5NKR (3,4-epoxy-1-butene) RN - 9007-49-2 (DNA) RN - EC 2.4.2.8 (Hypoxanthine Phosphoribosyltransferase) SB - IM MH - Animals MH - Benzo(a)pyrene/toxicity MH - DNA/genetics MH - *DNA Adducts MH - DNA Repair MH - DNA-Binding Proteins/*deficiency/genetics MH - Epoxy Compounds/*toxicity MH - Genes, Reporter/genetics MH - Hypoxanthine Phosphoribosyltransferase/*genetics MH - Mice MH - Mice, Knockout MH - Mutagens/*toxicity MH - Mutation EDAT- 2005/08/12 09:00 MHDA- 2006/04/25 09:00 CRDT- 2005/08/12 09:00 PHST- 2005/08/12 09:00 [pubmed] PHST- 2006/04/25 09:00 [medline] PHST- 2005/08/12 09:00 [entrez] AID - 10.1002/em.20169 [doi] PST - ppublish SO - Environ Mol Mutagen. 2006 Jan;47(1):67-70. doi: 10.1002/em.20169.