A comparison of induced mutation at homologous alleles of the tk locus in human cells

Abstract

Using a restriction fragment length polymorphism which can distinguish the two copies of the thymidine kinase (tk) gene in the TK6 human lymphoblastoid cell line, we have identified heterozygous subclones with alternate active alleles. Quantitative mutagenesis studies with X-rays revealed a markedly different response, depending on which homolog carried the active allele. The slopes of the dose-response curves differed by approximately 10-fold for mutation of the two alleles and this relationship held true for several independently isolated cell lines. Only one of the cell lines showed a different response to ethyl methanesulfonate. There were no differences among any of the cell lines at the X-linked hprt locus. Analyses of TK − mutants recovered from these cell lines indicated that the reduced yield of mutants from the one allele may be due, at least in part, to a lack of a specific class of TK − mutant, that is, the slow-growing mutants which have been associated with large-scale mutagenic events.