Mutagenesis in repair-deficient human cell strains

Cell killing and mutation experiments with a range of human skin fibroblast cell strains are described. With ultraviolet light increased sensitivity to cell killing was observed in excision-defective xeroderma pigmentosum cell strains and cells from Cockayne syndrome patients and patient 11961 from no known syndrome with no observable defects in repair. Xeroderma pigmentosum variant cells with defects in daughter strand repair did not show enhanced sensitivity. All of these cell strains were hypermutable when compared with normal cells and this allows the authors to propose that (i) excision repair may, as in bacteria, be essentially error free, (ii) daughter strand repair is error prone and (iii) additional undefined error-prone repair processes may exist. With gamma irradiation the sensitive ataxia telangiectasia cells are not hypermutable, these cells may then be defective in an error-prone repair process. Alternatively, induced mutants which have origin as chromosome deletions may prove lethal in such cells because of their susceptibility to the chromosome damaging effects of ionizing radiation. Photoreactivation was without effect on sister strand exchanges in a marsupial cell line. This result indicates that these chromosome effects are not caused by pyrimidine dimers but some other lesion. (Auth.)