Induction of p53 and increased sensitivity to cisplatin in ataxia-telangiectasia cells.
Several reports have demonstrated a defective p53 response to ionizing radiation exposure in ataxia-telangiectasia (A-T) cells. On the other hand, p53 induction was normal after u.v. irradiation, an agent to which A-T cells are not hypersensitive. We show here that A-T cells are more sensitive than normal lymphoblastoid cells to cisplatin treatment but the rate of induction of p53 by cisplatin is similar in both cell types. In addition, the half-life of p53, both in the induced and uninduced forms, is the same in A-T and normal lymphoblastoid cells. The use of a reporter assay to determine the functional status of p53 confirmed the results obtained in the induction experiments with cisplatin. These results demonstrate that p53 induction status in A-T cells does not correlate with sensitivity to the inducting agent and there is no inherent defect in the turn-over of p53 in the induced or uninduced states in A-T.
Zhang
N
N
Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Brisbane, Australia.
Song
Q
Q
Lu
H
H
Lavin
M F
MF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001260:Ataxia Telangiectasia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000502:physiology
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin