Evidence for coincident mutations in human lymphoblast clones selected for functional loss of a thymidine kinase gene.

摘要: A mitotic "recombination-competent state" inducible by x-irradiation is thought to exist in yeast. We sought evidence for such a process mammalian cells examining the occurrence of mutations at unlinked loci clones derived from human lymphoblast cell line. total 169 independent that arose spontaneously or after exposure x-rays ethyl methanesulfonate were selected new somatic thymidine kinase gene on chromosome 17q. They subsequently screened coincident use variable-number-of-tandem-repeat probes located different chromosomes. Three positively identified Southern analysis chromosomes 7 and 14; they included one produced allele two caused loss heterozygosity. Densitometric latter indicated presence copies remaining allele. Several possible genetic events also observed 17. These findings revealed mutant fraction about 10(-2)/cell, whereas expected mutation these less than 10(-4)/cell. results may thus provide first molecular "global" mutational capable inducing instability exists cells.