Modeling and measurement of the spontaneous mutation rate in mammalian cells

The study of spontaneous mutation rates in mammalian cells has been hampered by the lack of an alternative to the cumbersome Luria and Delbrück fluctuation test. A brief review of mathematical treatments of spontaneous mutagenesis, along with some of the limitations of the fluctuation test, is presented. A new experimental method and a simple mathematical model for deriving the spontaneous mutation rate are described. Data from the transgenic Chinese hamster G12 cell line growing at two different rates is analyzed according to this model. The results support the concept that, at least for growing cells, the spontaneous mutation rate is independent of the growth rate, and the mutant fraction increases in a linear fashion with the number of generations.