Induction and Characterization of Human Glioma Clones With Different Radiosensitivities

To facilitate investigation of the molecular mechanisms of tumor cell radiosensitivities, we have generated a set of clones with different radiosensitivities from a human glioma cell line U-251 MG-Ho. Forty-four colonies were isolated by subjecting parent cells to the mutagen N-methylnitrosourea and then irradiating these cells with increasing doses of x-rays. About half of the clones displayed different radiosensitivities than the parent cells. We selected one of the most sensitive clones ( ) ()X3i and one of the most resistant clones Y6 for further study. Isoeffective doses for these two clones differed by about a factor of 1.7; the relative radiosensi-tivities of both clones were stable for at least 30 cell culture passages. These two clones do not differ signif-icantly in either the induction or repair of radiation-in-duced DNA double-strand breaks as measured by pulsed field gel electrophoresis. Radiation-induced apoptosis measured by terminal deoxynucleotide trans-ferase-mediated dUTP nick end labeling assay and mi-cronucleus formation were similar in both clones. How-ever, potentially lethal damage repair was greater in the radioresistant Y6 clone than in the radiosensitive X3i clone as determined by colony-forming efficiency as-say