Effect of p53 on lung carcinoma cells irradiated by carbon ions or X-rays

The study is to investigate the feasibility and advantages of heavy ion beams on radiotherapy. The cellular cycle and apoptosis, cell reproductive death and p53 expression evaluated with flow cytometry, clonogenic survival assays and Western blot analysis were examined in lung carcinoma cells after exposure to 89.63 MeV/u carbon ion and 6 MV X-ray irradiations, respectively. The results showed that the number colonyforming assay of A549 was higher than that of H1299 cells in two radiation groups; A549 cellular cycle was arrested in G2/M in 12 h and the percentage of apoptosis ascended at each time point of carbon ion radiation with doses, the expression of p53 upregulated with doses exposed to X-ray or carbon ion. The cell number in G2/M of H1299 and apoptosis were increasing at all time points with doses in 12C6+ ion irradiation group. The results suggested that the effects of carbon ions or X rays irradiation on lung carcinoma cells were different, 12C6+ ion irradiation could have more effect on upregulating the expression of p53 than X-ray, and the upregulated expression of p53 might produce the cellular cycle G2/M arrested, apoptosis increasing; and p53 gene might affect the lung cancer cells radiosensitivity.

Potential role of DNA-dependent protein kinase in cellular resistance to ionizing radiation

In this paper,we study the ability of DNA-PK-deficient(M059J) and -proficient(M059K) cells to undergo the rate of cellular proliferation,cell cycle distribution and apoptosis after 10 Gy X-ray irradiation,and the role of DNA-PK in radiosensitivity.The results showed that M059J cells exhibited hyper-radiosensitivity compared with M059K cells.A strong G2 phase arrest was observed in M059J cells post irradiation.Significant accumulation in the G2 phase in M059J cells was accompanied by apoptosis at 12 h.Altogether,the data suggested that DNA-PK may have two roles in mammalian cells after DNA damage,a role in DNA DSB repair and a second role in DNA-damaged cells to traverse a G2 checkpoint,by which DNA-PK may affect cellular sensitivity to ionizing radiation.

Potentiality of phosphorylation of BRCA1 at Ser 1524 to activate p21 in response to X-ray irradiation

The breast and ovarian cancer susceptibility gene BRCA1 encodes a nuclear phosphoprotein, which functions as a tumor suppressor gene. Many studies suggested that multiple functions of BRCA1may contribute to its tumor suppressor activity, including roles in cell cycle checkpoints, apoptosis and transcription. It is postulated that phosphorylation of BRCA1 is an important means by which its cellular functions are regulated. In this study, we employed phospho-Ser-specific antibody recognizing Ser-1524 to study BRCA1 phosphorylation under conditions of DNA damage and the effects of phosphorylation on BRCA1 functions. The results showed that 10 Gy X-ray treatment significantly induced phosphorylation of Ser-1524 but not total BRCA1 protein levels. The expression both of p53 and p21 increased after irradiation, but ionizing radiation (IR) -induced activation of p21 was prior to that of p53. The percentages of G0/G1 phase remarkably increased after IR. In addition, no detectable levels of 89 kDa fragment of PARP, a marker of apoptotic cells, were observed. Data implied that IR-induced phosphorylation of BRCA1 at Ser-1524 might activate p21 protein, by which BRCA1 regulated cell cycle , but play no role in apoptosis.

Interpretation of Excess Power in Terms of Quasi－atom Multibody Exoergic Models

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Mouse Thymus Responses of Exposure to Low-dose Continuously Fractionated Whole Body X-ray Irradiation

Electromagnetism irradiation has a biological effectiveness for cell killing, cell cycle perturbations and genetic instability. The biological risks from space radiation encountered by cosmonauts were estimated for long term duration in space, such as the planned mission to Mars. Thymus as a very important immune organ has been studied frequently. We investigated the effects of exposure with low-dose continuously frac-

Alterations of Immune System Induced by ^(12)C^(6+) Heavy Ion Irradiation in Mice

High LET radiations, such as heavy ions or neutrons, have an increased biological effectiveness compared with low LET radiation for cell killing, cell cycle perturbations and genomic instability.

Anomalous Phenomena in E＜18keV Ion Beam Implantation Experiments on Pd and Ti

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BRCA1 and its phosphorylation involved in caffeine-inhibitable event upstream of G2 checkpoint

Caffeine,which specifically inhibits ATM/ATR kinases,efficiently abrogates the ionizing radiation(IR)-induced G2 arrest and increases the sensitivity of various tumor cells to IR.Mechanisms for the effect of caffeine remain to be elucidated.As a target of ATM/ATR kinases,BRCA1 becomes activated and phosphorylated in response to IR.Thus,in this work,we investigated the possible role of BRCA1 in the effect of caffeine on G2 checkpoint and observed how BRCA1 phosphorylation was regulated in this process.For these purposes,the BRCA1 protein level and the phosphorylation states were analyzed by Western blotting by using an antibody against BRCA1 and phospho-specific antibodies against Ser-1423 and Ser-1524 residues in cells exposed to a combination of IR and caffeine.The results showed that caffeine down-regulated IR-induced BRCA1 expression and specifically abolished BRCA1 phosphorylation of Ser-1524,which was followed by an override of G2 arrest by caffeine.In addition,the ability of BRCA1 to transactivate p21 may be required for MCF-7 but not necessary for Hela response to caffeine.These data suggest that BRCA1 may be a potential target of caffeine.BRCA1 and its phosphorylation are most likely to be involved in the caffeine-inhibitable event upstream of G2 arrest.