The thymidine-kinase locus of Friend erythroleukaemic cells. 1. Mutation rates and properties of mutants.

Spontaneous mutation at the thymidine-kinase locus in clone 707 of the Friend cell line has been examined. The rate of mutation in BrdU resistance was found to be 2.6 x 10(-6) cell-1 generation-1. The rate of reversion to HAT resistance was found to vary from 1.1 x 10(-7) to 2.85 x 10(-6) cell-1 generation-1 in 4 BrdU-resistant clones. Of 14 mutant clones assayed for thymidine-kinase activity only one had greater than 13% the activity of wild-type cells. Fluctuation analysis showed that mutations occurred spontaneously and were not induced by the selective agent. The mutation rate at the thymidine-kinase locus is several orders of magnitude greater than those reported for several other cells lines. There does not appear to be a general genetic instability in this cell line as the mutation rate at the HGPRT locus is similar to those found in other established cell lines. It is suggested that the high forward mutation rate at the thymidine-kinase locus may be due to only one functional thymidine-kinase allele being present in cells of this clone.