Estimation of mutation rates in cultured mammalian cells
| Autor: | Ernest H. Y. Chu, Jiliang Fu, I-Chian Li, Yung-Tai Hung |
|---|---|
| Rok vydání: | 1983 |
| Předmět: |
Genetics
Mutation rate Models Genetic Health Toxicology and Mutagenesis Mutant Biology Square (algebra) Cell Line Orders of magnitude (bit rate) Kinetics Distribution (mathematics) Cell culture Mutation Statistics Mutation (genetic algorithm) Test statistic Animals Humans Molecular Biology Cells Cultured Mathematics |
| Zdroj: | Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 111:253-262 |
| ISSN: | 0027-5107 |
| DOI: | 10.1016/0027-5107(83)90068-4 |
| Popis: | The factors that affect reliable estimations of mutation rates (g) in cultured mammalian somatic cell populations by fluctuation analysis are studied experimentally and statistically. We analyze the differential effect of the final cell population size in each culture (N t) and the number of parallel cultures (C) on the variation in the rate estimates (tl) inferred from the P0 method. The analysis can be made after the derivation of the variance of/i, which is a measure of variation of tl for a given combination of N t and C in a number of repeat experiments. The variance of ti is inversely proportional to C and to the square of N t. N t determines the probability of occurrence of mutations in a cell culture. By influencing the size of P0, Nt also determines whether a rate estimate is obtainable from the experiment. Since Po is estimated from the fraction of cultures containing no mutation in a set of C cultures, C becomes a determining factor for the accuracy of/2. The rate estimated from/5 o is biased, but the bias is in general 2 orders of magnitude smaller than /i. By the selection of an appropriate combination of N t and C for the experiment, this bias can be reduced even further. Based on the notion of comparing two proportions, we propose a test statistic and have applied it to experimental results for a test of equality of mutation rates in different cell lines. This development places the comparison of mutation rates on a statistical basis. Since the publication of Luria and Delbriick's paper [19] on the distribution of the number of mutant colonies in a series of parallel cultures, fluctuation analysis has been widely applied as a method for the determination of mutation rates (#) in cell populations. The analysis has since been further developed methodologically by Lea and Coulson [15], Newcombe [22], and Armitage [2,3] and modified theoreti |
| Databáze: | OpenAIRE |
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