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. W e have used human lung cancer cell lines carrying a plasmid vector containi ng a (CA)(13) microsatellite sequence to study frameshift mutations mediate d by ROS-generating chemicals paraquat and hydrogen peroxide. Exposure of t he cells to both paraquat and hydrogen peroxide resulted in significantly h igher 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 m utations 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 microsatel lite sequences in vivo.