Role of wild-type p53 in apoptotic and non-apoptotic cell death induced by X-irradiation and heat treatment in p53-mutated mouse M10 cells.
The sensitizing effects of wild-type p53 on X-ray-induced cell death and on heat-induced apoptosis in M10, a radiosensitive and Trp53 (mouse p53 gene)-mutated lymphoma cell line which dies through necrosis by X-irradiation, were investigated using three M10 derived transfectants with wild-type TP53 (human p53 gene). Cell death was determined by colony formation and/or dye exclusion test, and apoptosis was detected as the changes in nuclear morphology by Giemsa staining. Expression of wild-type p53 protein increased radiosensitivity of cell death as determined by both clonogenic and dye exclusion assays. This increase in radiosensitivity was attributable largely to apoptosis induction in addition to a small enhancement of necrosis. Interestingly neither pathway to cell death was accompanied by caspase-3 activation. On the other hand, heat-induced caspase-3 dependent apoptotic cell death without transfection was further increased by the transfection of wild-type p53. In conclusion, the introduction of wild-type p53 enhanced apoptotic cell death by X-rays or heat via different mechanisms that do or do not activate caspase-3, respectively. In addition, p53 also enhanced the X-ray-induced necrosis in M10 cells.
Department of Nuclear Engineering, School of Engineering, Tokai University, Hiratsuka-shi, Kanagawa, Japan. aeito@keyaki.cc.u-tokai.ac.jp
Atsushi
A
Ito
Hisako
H
Nakano
Kunio
K
Shinohara
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects*; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000235:genetics / Q000502:physiology / Q000528:radiation effects; D045744:Cell Line, Tumor; D016158:Genes, p53; D006358:Hot Temperature; D006801:Humans; D051379:Mice; D009154:Mutation; D009336:Necrosis; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000502:physiology*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C505409:Casp3 protein, mouse; D053148:Caspase 3