Different inducibility of radiation- or heat-induced p53-dependent apoptosis after acute or chronic irradiation in human cultured squamous cell carcinoma cells.
OBJECTIVE
This study was undertaken to clarify the effects of acute or chronic pre-irradiation on the induction of p53-dependent apoptosis by X-rays or heat shock.


METHODS
Having an identical genotype except for p53-status, the human cultured squamous cell carcinoma cells (SAS) were transfected with a mutant p53 gene (SAS/mp53) or neo alone (SAS/neo) as a control. After acute X-irradiation (1 Gy min(-1)), chronic gamma-irradiation (0.001 Gy min(-1)) or heat shock (44 degrees C), the cells were for the incidence of apoptotic bodies and DNA ladders, cellular levels of p53 and bax, and caspase-3 activity.


RESULTS
It was found that (1) a challenge treatment with X-rays (5.O Gy) or heat shock (30 min) immediately after chronic pre-irradiation (1.5 Gy) but not acute pre-irradiation (1.5 Gy) resulted in lower levels of apoptosis than those observed after challenge treatment only in SAS/neo cells; (2) a challenge treatment-induced apoptosis was observed 48 h after cessation of chronic pre-irradiation in SAS/neo cells; (3) apoptosis was barely increased in SAS/mp53 cells; and (4) the levels of apoptosis-related proteins after challenge treatments were strongly correlated with the above phenomena.


CONCLUSIONS
Chronic pre-irradiation at a low dose-rate suppressed induction of p53-dependent apoptosis via bax and caspase-3. These findings suggest that chronic pre-irradiation suppressed p53 function through radiation-induced signalling and/or p53 stability.
Department of Biology, Nara Medical University, Kashihara, Japan. atakahas@naramed-u.ac.jp
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Takahashi
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D016158:Genes, p53 / Q000235:genetics; D006358:Hot Temperature; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D013696:Temperature; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism*; D014965:X-Rays; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases