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 radiosensitivities of both clones were stable for at least 30 cell culture passages. These two clones do not differ significantly in either the induction or repair of radiation-induced DNA double-strand breaks as measured by pulsed field gel electrophoresis. Radiation-induced apoptosis measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay and micronucleus formation were similar in both clones. However, potentially lethal damage repair was greater in the radioresistant Y6 clone than in the radiosensitive X3i clone as determined by colony-forming efficiency assay.
Brain Tumor Research Center of the Department of Neurological Surgery, School of Medicine, University of California, San Francisco 94143-0520, USA.
J
J
Wang
L
L
Hu
N
N
Gupta
T
T
Shamseldin
T
T
Ozawa
J
J
Klem
M
M
Cardell
D F
DF
Deen
D000477:Alkylating Agents; D017209:Apoptosis / Q000528:radiation effects; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000528:radiation effects; D002875:Chromosomes / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005910:Glioma / Q000139:chemically induced / Q000532:radiotherapy*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008770:Methylnitrosourea; D015162:Micronucleus Tests; D011836:Radiation Tolerance; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014965:X-Rays
D000477:Alkylating Agents; D008770:Methylnitrosourea