The estimation of in vivo mutation rate and frequency samples of human lymphocytes

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Abstract

In vivo mutation assays usually involve enumeration of mutant cells in samples drawn from individuals or populations, and inferences concerning quantitative aspects of mutation are made from the results. Individual cells within the samples may show clonal relationships with each other. For populations of constant size, which do not obey Luria-Delbruck kinetics, mutation frequency should be calculated from the number of mutant cells and not from the number of mutant clones. The change in mutation frequency/unit time provides the best estimate of the mutation rate, which for human T lymphocytes is approx. 2.0 x 10-9 mutations/cell/day, a rate higher than that explicable by proliferation alone. Since lymphocyte populations in vivo contain uncommon large clones, the statistics of rare events results in all measured mutant frequencies for individuals being affected by discontinuous variation. The presence or absence of a large mutant clone in an individual results in the measured MF being either a large overestimate of the population MF in a minority of individuals or a small underestimate in the majority of individuals. An adjusted mutation frequency can be calculated to eliminate this source of variation but this is rarely necessary.

Original languageEnglish
Pages (from-to)167-176
Number of pages10
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume357
Issue number1-2
DOIs
Publication statusPublished - 25 Oct 1996
Externally publishedYes

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