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Genome Maintenance and Mutagenesis in Embryonic Stem Cells
Qing Lin, Sarah L Donahue and H Earl Ruley
volume 5 | issue 23
1 december 2006Pages: 2710 - 2714
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Widespread loss of heterozygosity (LOH) in cancer cells is often thought to result from chromosomal instability caused by mutations affecting DNA repair/genome maintenance; however, the origin of LOH in most tumors is unknown. In a recent study, we examined the ability of carcinogenic agents to induce LOH in diploid mouse embryo-derived stem (ES) cells. Brief exposures to non-toxic levels of several carcinogens stimulated genome-wide LOH, with maximum per-gene frequencies approaching one percent. These results suggest that LOH contributes significantly to the carcinogenicity of a variety of mutagens, and that genome-wide LOH may result from prior exposure to genotoxic agents rather than from a state of chromosomal instability during the carcinogenic process. Mechanisms in stem cells that influence carcinogen-induced LOH are likely to play central roles in the etiology of non-hereditary cancers that often arise after extensive carcinogen exposures.
Authors
Qing Lin
Vanderbilt University, School of Medicine, Nashville, TN
Sarah L Donahue
Vanderbilt University, School of Medicine, Nashville, TN
H Earl Ruley
Vanderbilt University, School of Medicine, Nashville, TN
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.