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3,4‐Epoxy‐1‐butene, a reactive metabolite of 1,3‐butadiene, induces somatic mutations in Xpc ‐null mice
Author(s) -
Wickliffe J.K.,
Galbert L.A.,
Ammenheuser M.M.,
Herring S.M.,
Xie J.,
Masters O.E.,
Friedberg E.C.,
Lloyd R.S.,
Ward J.B.
Publication year - 2006
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.20169
Subject(s) - dna damage , nucleotide excision repair , dna repair , carcinogen , chemistry , microbiology and biotechnology , dna , in vivo , 1,3 butadiene , hypoxanthine guanine phosphoribosyltransferase , guanine , mutant , genetics , biology , biochemistry , nucleotide , gene , catalysis
Xpc ‐null ( Xpc −/− ) mice, deficient in the global genome repair subpathway of nucleotide excision repair (NER‐GGR), were exposed by intraperitoneal (IP) 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 IP 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. Environ. Mol. Mutagen., 2006. © 2005 Wiley‐Liss, Inc.