3,4-Epoxy-1-butene, a reactive metabolite of 1,3-butadiene, induces somatic mutations in Xpc-null mice

Jeffrey K. Wickliffe, L. A. Galbert, M. M. Ammenheuser, S. M. Herring, J. Xie, O. E. Masters, E. C. Friedberg, R. S. Lloyd, J. B. Ward

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)67-70
Number of pages4
JournalEnvironmental and Molecular Mutagenesis
Volume47
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

Keywords

  • Benzo[a]pyrene
  • Butadiene
  • Epoxybutene
  • Hprt
  • Nucleotide excision repair
  • Xpc

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)
  • Health, Toxicology and Mutagenesis

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    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. (2006). 3,4-Epoxy-1-butene, a reactive metabolite of 1,3-butadiene, induces somatic mutations in Xpc-null mice. Environmental and Molecular Mutagenesis, 47(1), 67-70. https://doi.org/10.1002/em.20169