Decreased deletion mutation in radioadapted human lymphoblasts

Abstract

Survival and HPRT- mutant frequency were measured in human lymphoblastoid cells preexposed or not to a low dose of 0.02 Gy gamma rays and then treated with a high dose of 4.0 Gy. When compared to the high dose alone, the low-dose preexposure induced a 70% reduction of the mutant frequency, whereas cell survival was not affected. To understand the mechanisms underlying this phenomenon, the molecular nature of an HPRT- mutant collection was established using Southern hybridization analysis. Among mutants induced by irradiation with the high dose alone, 78% (21/27) had detectable alterations of the HPRT gene. In contrast, only 42% (15/26) of mutants which were "adapted" by the low-dose exposure were of this type. Moreover, the fraction of mutants with only partial deletions of the HPRT gene was significantly reduced (52 and 19% for the 4.0 Gy and 0.02 Gy plus 4.0 Gy induced mutant sets, respectively). In other words, the mutational specificity differed, depending on whether or not the cells were adapted. We suggest that low-dose preexposure leads to a reduced susceptibility to the mutagenic effect of a high dose of gamma rays by inducing an error-free repair system. Our data indicate that this putative system acts preferentially on the class of premutagenic lesions which produce deletions.