Elevated spontaneous mutation rate in Bloom syndrome fibroblasts.

Abstract
The rates of spontaneous mutation to 6-thioguanine resistance were determined in fibroblasts derived from normal and two Bloom syndrome individuals (GM 2548 and GM 1492). Two methods were utilized to determine the rates. Method I obtained the spontaneous mutation rate from the increase in the mutation frequency of a cell population in logarithmic-phase growth over 10 days. The two Bloom syndrome strains had spontaneous mutation rates of 16 X 10(-6) and 17 X 10(-6) mutations per cell per generation, whereas two normal strains had rates of 1.5 X 10(-6) and 1.1 X 10(-6). Method II utilized fluctuation analysis to measure the rate of spontaneous mutation. This method resulted in rates of 19 X 10(-6) and 23 X 10(-6) mutations per cell per generation in Bloom syndrome cells, compared to rates of 4.6 X 10(-6) and 4.9 X 10(-6) in the control strains. These data suggest that Bloom syndrome may be a mutator mutation, a previously unrecognized phenomenon in humans, and that an elevated spontaneous mutation rate in vivo may be responsible for the clinical phenotype of primordial dwarfism and increased cancer incidence.

This publication has 43 references indexed in Scilit: