Induction of microsatellite mutations by oxidative agents in human lung cancer cell lines.
Genomic instability has been associated with cancer development. Oxidative DNA damage seems to contribute to genetic instability observed in cancer. We have used human lung cancer cell lines carrying a plasmid vector containing a (CA)(13) microsatellite sequence to study frameshift mutations mediated by ROS-generating chemicals paraquat and hydrogen peroxide. Exposure of the cells to both paraquat and hydrogen peroxide resulted in significantly higher mutation frequencies compared with untreated control cells. Mutation frequencies up to 27-fold higher than the spontaneous mutation frequencies were obtained. The majority of the reversion mutants contained frameshift mutations within the target sequence. However, the pattern of deletions and additions was significantly different in the two cell lines. These results indicate that oxidative damage may play a role in instability of microsatellite sequences in vivo.
Zienolddiny
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S
Department of Toxicology, National Institute of Occupational Health, PO Box 8149 Dep., N-0033 Oslo, Norway.
Ryberg
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D
Haugen
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A
D002934:Cinnamates; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D016368:Frameshift Mutation; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000633:toxicity*; D006921:Hygromycin B / Q000031:analogs & derivatives / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics*; D018895:Microsatellite Repeats; D009355:Neomycin / Q000494:pharmacology; D016877:Oxidants / Q000633:toxicity*; D010269:Paraquat / Q000378:metabolism / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016364:Reading Frames / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002934:Cinnamates; D004273:DNA, Neoplasm; D016877:Oxidants; D017382:Reactive Oxygen Species; D006921:Hygromycin B; C026273:hygromycin A; D006861:Hydrogen Peroxide; D009355:Neomycin; D010269:Paraquat