A gamma-ray-resistant derivative of an ataxia telangiectasia cell line obtained following DNA-mediated gene transfer.

Genomic DNA from normal human or mouse cells was transfected together with the selectable marker gpt into the simian virus 40-transformed ataxia telangiectasia fibroblast line, AT5BIVA. From a series of experiments involving over 400,000 clones selected for the gpt marker, one unambiguously radiation-resistant clone (clone 67) was recovered following selection with repeated cycles of gamma irradiation. The normal level of radiation resistance of clone 67 has been maintained for at least 11 months in the absence of further selection by radiation. The resistant clone contains one copy of the gpt gene. Its DNA synthesis following gamma-irradiation is inhibited to an extent intermediate between that of ataxia telangiectasia and normal cells. Three out of four thioguanine-resistant derivatives of clone 67 have either lost or do not express the gpt sequence and show almost the same sensitivity to gamma irradiation as the original AT5BIVA line. This suggests that the radiation resistance of clone 67 may be linked to the gpt sequence and may have arisen as a consequence of the transfection, rather than as the result of an independent mutation to radiation resistance.