Isolation of radiosensitive and radioresistant mutants from a medulloblastoma cell line.
Two mutant clones, one radiosensitive (OS-3) and one resistant (OR-5), were isolated from ONS-76 after screening 2400 clones by the replica micro-well technique. These two clones exhibited significantly different radiosensitivity, with D37 values of 4.7Gy in OR-5 and 1.7Gy in OS-3. After gamma irradiation (8Gy), OR-5 exhibited greater G2 arrest than sensitive clone OS-3. Administration of 5mM of caffeine resulted in greater cell killing in OR-5 than in OS-3, with an almost complete release of G2 block. These observations support the notion that the G2 block contributes to the repair process of DNA damage after irradiation. The present results suggest that clones with a large postirradiation G2 block may show a greater reduction in radiosensitivity if the G2 block is released artificially. The study of the mutant clones described herein may provide important clues to the mechanism by which glioma cells acquire radioresistance.
Tsuboi
K
K
Department of Neurological Surgery, University of Tsukuba, Ibaraki, Japan. tsuboi@igaku.md.tsukuba.ac.jp
Tsuchida
Y
Y
Endo
K
K
Yoshii
Y
Y
Nose
T
T
D002110:Caffeine / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism*; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011836:Radiation Tolerance / Q000502:physiology*; D014407:Tumor Cells, Cultured
D002110:Caffeine; D004247:DNA