title: In vitro phenotype of ataxia-telangiectasia (AT) fibroblast strains: clues to the nature of the "AT DNA lesion" and the molecular defect in AT.
abstract: Studies of the in vitro phenotype of a series of AT strains established in Israel revealed the following features: premature senescence and increased demands for growth factors, normal sensitivity to the cytotoxic effect of alkylating agents, hypersensitivity to agents that damage the deoxyribose moiety of DNA via a "targeted" free radical attack (this hypersensitivity is coupled with reduced inhibition of DNA synthesis compared to normal cells), varying degrees of intermediate hypersensitivity to the same agents in AT heterozygous cells, lack of potentially lethal damage repair and sublethal damage repair in AT homozygous cells following treatment with free radical-producing agents. We conclude that AT involves a DNA repair defect and that the AT DNA lesion is probably a gap with the 3'-phosphate or 3'-phosphoglycolate end left in the DNA following sugar destruction.
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D001260:Ataxia Telangiectasia / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D004260:DNA Repair; D004261:DNA Replication; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006579:Heterozygote; D006801:Humans; D010641:Phenotype; D011836:Radiation Tolerance
chemical_list: D000477:Alkylating Agents