3,4-Epoxy-1-butene, a reactive metabolite of 1,3-butadiene, induces somatic mutations in Xpc-null mice
| Autor: | Jingwu Xie, O. E. Masters, Jeffrey K. Wickliffe, Errol C. Friedberg, Jonathan B. Ward, L. A. Galbert, S. M. Herring, R. S. Lloyd, Marinel M. Ammenheuser |
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| Rok vydání: | 2005 |
| Předmět: |
Hypoxanthine Phosphoribosyltransferase
DNA Repair Epidemiology DNA damage DNA repair Health Toxicology and Mutagenesis Metabolite Mutagen Biology medicine.disease_cause chemistry.chemical_compound DNA Adducts Mice In vivo Genes Reporter medicine Benzo(a)pyrene Animals Genetics (clinical) Mice Knockout DNA Molecular biology DNA-Binding Proteins chemistry Mutation Epoxy Compounds Nucleotide excision repair Mutagens |
| Zdroj: | Environmental and molecular mutagenesis. 47(1) |
| ISSN: | 0893-6692 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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