Journal Article

Induction of microsatellite mutations by oxidative agents in human lung cancer cell lines

Shanbeh Zienolddiny, David Ryberg and Aage Haugen

in Carcinogenesis

Volume 21, issue 8, pages 1521-1526
Published in print August 2000 | ISSN: 0143-3334
Published online August 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.8.1521
Induction of microsatellite mutations by oxidative agents in human lung cancer cell lines

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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.

Keywords: CFE, colony forming efficiency; H2O2, hydrogen peroxide; Hyg, hygromycin; Hyg B, hygromycin phosphotransferase B; MSI, microsatellite instability; neo, neomycin; PBS, phosphate-buffered saline; ROS, reactive oxygen species.

Journal Article.  4576 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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