Mevalonate deprivation leads to aneuploidy in Chinese hamster ovary cells.
After exposure to compactin, the competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 22% of CHO-K1 cells contained abnormally high numbers of chromosomes. In two populations of cells selected for compactin resistance 31 and 33% of the cells contain more than 22 chromosomes. Some cell lines isolated from these populations have the wild type chromosome number of 20-21, while others have a broad distribution of chromosome number, often with a mean around 36-40. Finally, Chinese hamster ovary cells that are mutant for 3-hydroxy-3-methylglutaryl-CoA reductase and therefore auxotrophic for mevalonate were starved for that compound. This treatment also increased the number of cells containing extra chromosomes. These results indicate that interruption of the cellular supply of mevalonate results in abnormal chromosome number.
Department of Biological Sciences, Stanford University, California 94305-5020.
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D000782:Aneuploidy; D000818:Animals; D002460:Cell Line; D002875:Chromosomes / Q000187:drug effects*; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008798:Mevalonic Acid / Q000502:physiology*; D009154:Mutation; D010053:Ovary
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C012258:mevastatin; D004247:DNA; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid