| MIN Feng-ling,ZHANG Hong,LI Wen-jian.Cell death pathways of melanoma cells induced by irradiation at different LET combined with p53 gene therapy[J].Chinese Journal of Radiological Medicine and Protection,2008,28(3):238-241 |
| Cell death pathways of melanoma cells induced by irradiation at different LET combined with p53 gene therapy |
| Received:June 03, 2007 |
| DOI： |
| KeyWords:p53 gene Carbon-ion beams LET Cell death Melanoma |
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| Abstract:: |
| Objective To investigate the effect of exogenous wild type P53 on the radiation induced cells apoptosis and necrosis at different levels of linear energy transfer (LET), and evaluate its mechanisms. Methods The human melanoma cell line A375, with wild-type p53 gene was used, as well as the transfectant A375 cells (A375/p53) with adenoviral vector containing the wild-type p53 gene. These cells were exposed to X-rays and accelerated carbon-ion(C-) beams. Cellular radiosensitivity was determined by using clonogenic assay. Apoptotic and necrotic cell death rate was determined morphologically by dual-staining (acridine orange, ethidium bromide) for fluorescence microscope. Results 1 There was no significant difference in survival fraction between A375 cells and A375/p53 cells irradiated by C-beams with greater than 32 KeV/μm. 2 Apoptosis rates in the two kinds of cells increased in a LET-dependent manner, exogenous wild-type P53 induced cell apoptosis more efficiently in A375/p53 than that in A375 cells with X-rays or high-LET irradiation. 3 The necrosis rates in A375 cells exposed to high-LET irradiation increased significantly (P<0.05) in comparison with A375/p53 cells. Conclusions Apoptosis induction is p53 dependent partly by high-LET irradiation, and exogenous wild-type P53 plays an important role in modulating cell death type, although there was no significant difference in cellular radiosensitivities. The observation in the study indicates the potential application of high-LET radiation combined with p53 in the management of human melanoma. |
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