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Enhanced radiosensitivity of cultured fibroblasts from ataxia telangiectasia heterozygotes manifested by defective colony-forming ability and reduced DNA repair replication after hypoxic. gamma. -irradiation. [/sup 60/Co]

Journal Article · · Cancer Res.; (United States)
OSTI ID:6551173
We have measured the sensitivity to ..gamma..-ray inactivation of diploid skin fibroblasts cultured from 10 persons in four families with ataxia telangiectasia (AT). Persons heterozygous for AT, including parents of afflicted patients, are not as yet detectable by any specific clinical or laboratory marker but are believed to constitute a substantial portion of the middle-aged cancer population. In one AT family, fibroblast strains from both parents exhibited a colony-forming ability after hypoxic irradiation which was intermediate between that displayed by five control strains from normal children and that from the affected child. In the remaining three families, cultures from only one parent were available; one parental strain displayed an intermediate survival capacity as above, whereas the other two responded normally. The homozygous recessive strains from the five afflicted children in the four families were all equally hypersensitive to hypoxic ..gamma..-ray inactivation. The three presumed AT heterozygous strains that displayed intermediate rayiosensitivity also carried out ..gamma..-rad-induced DNA repair replication to an extent intermediate between those in normals and AT homozygotes. These findings suggest that a numerically significant, cancer-prone subpopulation of humans carrying one normal and one abnormal AT gene may also be moderately sensitive to lethal effects of hypoxic ..gamma..-rays due to a defect in the enzymatic repair of DNA.
Research Organization:
Chalk River Nuclear Labs., Ontario
OSTI ID:
6551173
Journal Information:
Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 39; ISSN CNREA
Country of Publication:
United States
Language:
English