Similar repair of O⁶-methylguanine in normal and ataxia-telangiectasea fibroblast strains. Deficient repair capacity of lymphobalstoid cell lines does not reflect a genetic polymorphism

The ability of human fibroblast strains to repair the mutagenic DNA adduct O⁶-methylguanine (MNNG) was investigated. The repair reaction proceeded rapidly during the first hour after alkylation, followed by a slow, continuous phase of repair, and both processes were saturated by low doses of carcinogen. This was similar to what had previously been found in human lymphoblastoid lines. Three fibrobalst strains from healthy donors and six strains from patients with ataxia telangiectasia were all proficient in their capacity to repair O⁶-MeG and had the same sensitivity to the cytotoxicity of MNNG and methyl methanesulphonate as normal cells. Three of these cell strains were derived from individuals whose lymphoblastoid lines were deficient in their ability to repair O⁶-MeG. These lymphoblastoid lines were also extremely hypersensitive to killing by methylating carcinogens. Because non-transformed cells from the same donors behaved normally with regard to both parameters, we concluded that the repair deficiency accompanied by carcinogen hypersensitivity of the lymphoblastoid lines does not indicate a genetic deficiencu in the donor. These findings imply that lymphoblastoid lines may not always nbe the appropriate cell type for investigating genetic susceptibility to chemical mutagens.