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The prevalence of multilocus lesions in radiation-induced mutants

Journal Article · · Radiation Research; (United States)
DOI:https://doi.org/10.2307/3578804· OSTI ID:6741140
 [1]
  1. Case Western Reserve Univ., Cleveland, OH (United States)
In L5178Y mouse lymphoblasts, ionizing radiation-induced mutant frequencies were dramatically higher when the genetic marker analyzed was heterozygous (tk[sup +]/tk[sup [minus]]) than when hemizygous (tk[sup +]/tk[sup 0] or hprt[sup +]/hprt[sup 0]). In contrast, base-change mutagens induced similar mutant frequencies at heterozygous and hemizygous loci. These results indicate that the majority of radiation-induced mutants harbor multilocus lesions, and that these mutants are poorly recovered when the target gene is in a hemizygous chromosomal region. Dose-rate dependence of radiation-induced mutant frequency was demonstrated at the heterozygous tk locus but not at the hemizygous hprt locus; in a cell line deficient in the rejoining of DNA double-strand breaks (DSBs), no dose-rate dependence was observed for either locus. The major of TK[sup [minus]/[minus]] mutants, whether spontaneous or induced by X, [alpha]-particle or UV radiation, or by photosensitization, showed loss of the entire active tk allele. The percentage of TK[sup [minus]/[minus]] mutants exhibiting inactivation of galactokinase, encoded by the neighboring gk gene, was high in UV repair-deficient cells exposed to UV radiation and in DNA DSB repair-deficient lines exposed to X radiation. Thus the presence of unrepaired DNA lesions, whether DSBs or pyrimidine dimers, appears to result in an increase in the percentage of mutants harboring multilocus lesions. 52 refs., 15 figs., 2 tabs.
DOE Contract Number:
AC02-77EV04472; FG02-88ER60658
OSTI ID:
6741140
Journal Information:
Radiation Research; (United States), Journal Name: Radiation Research; (United States) Vol. 137:2; ISSN RAREAE; ISSN 0033-7587
Country of Publication:
United States
Language:
English