DNA fragility and repair capability are separate genetic phenotypes - studies on in-situ nick translation and...

Three separate experiments, designed to minimize the DNA repair process following exposures to mutagens, were performed to determine whether DNA repair capability is the sole factor responsible for differential mutagen sensitivity. These experiments included (i) very short bleomycin pulse treatments (2, 5 and 10 min), (ii) ionizing irradiation and (iii) bleomycin treatment with DNA repair inhibited by ethanol. Three lymphoblastoid cell lines, derived (i) from a patient with ataxia telangiectasia (AT), (ii) a patient with lupus erythematosus and (iii) a normal blood donor, were used as test cells. Mutagen sensitivity was measured either by the frequency of chromatid breaks or by grain counts in in situ nick translation preparations. In all cases, sensitivity rating followed the same pattern: AT>lupus>normal. The results support the notion that mutagen sensitivity may depend on two separate phenotype: intrinsic DNA fragility and repair capability.