Persistently elevated frequency of spontaneous mutations in progeny of CHO clones surviving X-irradiation: association with delayed reproductive death phenotype

Certain clonal progeny of Chinese hamster ovary (CHO) cells surviving X-irradiation demonstrate pleomorphic changes including a persistently decreased cloning efficiency, a dominant phenotype we have termed delayed reproductive death (Chang and Little, 1991, 1992b). We now report that cells from these progeny clones show a persistently elevated frequency of spontaneous mutations at the hprt locus for up to 95-100 population doubling post-irradiation. Mutant fractions as high as 10^-3 were scored, more than two orders of magnitude higher than those observed in clonal progeny of non-irradiated cells studied in parallel. These results are discussed in terms of the hypothesis that radiation induces a type of genetic instability among some surviving cells that results in a heritable mutator phenotype, and that this instability may also be involved in the phenomenon of delayed reproductive death.