| Popis: |
In their classic paper which demonstrated the preadaptive origin of phage resistance in bacteria, Luria and Delbriick (1943) proposed the use of the fluctuation test to estimate mutation rates in a bacterial population. Subsequently, a number of investigators have examined this problem from various angles, including formal derivations (Newcombe, 1948), mathematical models (Stocker, 1949), mutant distribution (Lea and Coulson, 1950) and statistical theories (Armitage, 1952, 1953). The study in this problem has been continued until recently (Kondo, 1972; Gilbert, 1980), all dealing with the formulae and methods for estimating mutation rates in bacteria. Since the initial demonstration of experimental mutagenesis in cultured mammalian cells (Chu and Malling, 1968; Kao and Puck, 1968), fluctuation analysis has been applied for quantitative estimation of mutation rates (Shapiro et al., 1972; Morrow, 1975). There has nevertheless been a great disparity among published rate estimates from experiments with a variety of cells and genetic marker systems; using the same genetic marker in the same cell types, differences in mutation rates have even been found in different experiments by the same laboratory. For instance, Albertini and DeMars (1973) estimated the spontaneous mutation rate to 8-azaguanine resistance in human diploid fibroblasts and obtained values in 5 Expts. varying by a factor of 14 (0.788 x 10 6 to 1.115 x 10 -5 per cell per generation. There are at least 3 sources of error that may be responsible for such differences. The most obvious would be the sampling error, but it is too big a range of values to be the sole source. The second source of error may be biological, which has been described in some detail by Abbondandolo (1977). The third type of error may originate from differences in experimental design. There are at least 5 different methods for the estimation of mutation rates, namely, the mean, the upper quartile, the median, the Po and the maximum likelihood methods (Luria and Delbr~ick, 1943; Newcombe, 1948; Lea and Coulson, 1950; Armitage, 1952; 1953; Kondo |
