Ionizing radiation signature mutations in human cell mutants induced by low-dose exposures

Investigation of mutational specificity at low doses has generally not been possible since the number of induced mutants may be similar or significantly lower than the spontaneous background. The use of a low-dose fractionated exposure protocol in TK6 human lymphoblasts results in an incremental accumulation of mutants induced by individual 20 cGy gamma-ray exposures. Therefore, the frequency of induced mutants within a population at the conclusion of a fractionated exposure regimen is sufficiently elevated to permit the recovery of a low-dose mutant collection. Statistical analysis of the data identified no significant differences between mutants induced by 20 or 200 cGy. However, deletions encompassing one or more Xq26 STS markers flanking the hprt locus represented only 1/107 (0.009) spontaneous HPRT- mutants but 34/170 (0.20) mutants induced by 20 or 200 cGy of ionizing radiation (P < 0.0001). The data presented here demonstrate that mutational fingerprints can be effectively defined using deletion mapping for clastogens such as ionizing radiation, and that the radiation-induced mutational spectrum is independent of dose.