The prevalence of multilocus lesions in radiation-induced mutants
Journal Article
·
· Radiation Research; (United States)
- 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
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Related Subjects
550200 -- Biochemistry
560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
DISEASES
DNA
DOSE-RESPONSE RELATIONSHIPS
GENES
IMMUNE SYSTEM DISEASES
LYMPHOMAS
MAMMALS
MICE
MUTANTS
MUTATION FREQUENCY
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PYRIMIDINE DIMERS
RADIATION INDUCED MUTANTS
RODENTS
STRAND BREAKS
VERTEBRATES
560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
DISEASES
DNA
DOSE-RESPONSE RELATIONSHIPS
GENES
IMMUNE SYSTEM DISEASES
LYMPHOMAS
MAMMALS
MICE
MUTANTS
MUTATION FREQUENCY
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PYRIMIDINE DIMERS
RADIATION INDUCED MUTANTS
RODENTS
STRAND BREAKS
VERTEBRATES