Differential locus sensitivity to mutation induction by ionizing radiations of different LETs in Chinese hamster ovary K1 cells

Abstract

Mutation induction after exposures to 250 kVp X-rays, alpha-particles from the radon daughter 212Bi, and fission-spectrum neutrons from the JANUS reactor was studied in Chinese hamster ovary (CHO) K1 cells and in CHO-10T5, a K1 derivative containing the bacterial gene xanthine-guanine phosphoribosyl transferase (gpt). Mutation induction was analyzed at three genetic loci: the gpt locus, the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus, and the thymidine kinase (tk) locus. After X-irradiation, mutants were induced at the tk loci at approximately 8-9 times the rate of mutant induction at the hprt locus, and the rate of mutant induction at the gpt locus was 8-10 times greater than that at the hprt locus. Neutron and alpha-radiation were more effective mutagenic agents. Mutant frequencies were approximately 4- to 6-fold higher than for X-rays at the hprt and gpt loci and greater than 12-fold greater than X-rays at the tk locus. The greater sensitivity of the tk locus to mutation induction by ionizing radiation (especially neutron and alpha-particle radiation) compared to the hprt locus is likely to be due to the recovery of an additional class of mutants, possibly ones containing larger-sized mutational events. Approximately half of the X-ray-induced tk-1- mutants were small-colony mutants, and 75% of the alpha- and neutron-induced tk-1- mutants were small-colony mutants. The increase in the proportion of small-colony mutants seen with increasing radiation linear energy transfer (LET) suggests that the radiation quality influenced the type of mutation recovered at this locus. There is probably a different reason for the hypersensitivity of the gpt locus because the frequency of gpt mutants, compared to the hprt locus, was independent of radiation quality. Therefore, the LET dependence of mutant induction is gene specific and not necessarily related to the size of deletion recoverable.