Showing papers by "Yosef Shiloh published in 1981"

Kinetics of O6-methylguanine repair in human normal and ataxia telangiectasia cell lines and correlation of repair capacity with cellular sensitivity to methylating agents.

Abstract: Human lymphoblastoid cell lines from normal individuals and from patients with ataxia telangiectasia were either proficient or deficient in their ability to repair the mutagenic DNA adduct O 6-methylguanine that is induced by methylating carcinogens. There was no relationship between the capacity to repair O 6-methylguanine and the ataxia telangiectasia phenotype. Time-course studies done following a short pulse (2 min) of alkylation with 0.5 µg of N -[3H]methyl- N′ -nitro- N -nitrosguanidine per ml revealed that the repair of O 6-methylguanine in human lymphoblastoid lines proficient in this ability is a rapid process, which proceeds with a half-life of 10 to 15 min. Lymphoblastoid lines with deficient capacity to repair this DNA adduct were hypersensitive to the cytotoxic effect of the methylating carcinogens N -methyl- N′ -nitro- N -nitrosoguanidine, N -methyl- N -nitrosourea, and methyl methanesulfonate, and this hypersensitivity was correlated with the relative amount of O 6-methylguanine induced by each of the three chemicals. This was taken as an indication of the lethality of unrepaired O 6-methylgluanine. The extent of DNA repair synthesis induced by the three carcinogens was the same in cell lines proficient and deficient in O 6-methylguanine repair, indicating no major deficiency in an excision repair pathway in the hypersensitive cell lines.