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.
LI NingZHANG HongWANG YanlingWANG XiaohuHAO JifangZHAO Weiping
This study investigated the impact of simulated microgravity on acute injury induced by low doses of carbon ions in male reproductive organs of mice,and determined alterations in spermatogenic function and expression levels of apoptotic factors in mice following exposure to acute irradiation after 7 days of simulated microgravity.The results demonstrated that significant reductions in spermatozoa,primary spermatocytes and spermatogonia,and increased globular cells in seminiferous tubule and pro-apoptotic proteins were observed in the group exposed to over0.4 Gy irradiation.Collectively,the data suggest that lesions inflicted by simulated microgravity are not markedly modified by lower doses of irradiation(0.2 Gy)in mouse testis compared to the control group.However,testicular impairments were markedly evident in the group exposed to higher doses of carbon ions plus simulated microgravity,which may be due at least in part to elevated apoptosis initiated by the mitochondrial apoptosis pathway in germ cells.
LIU YangZHANG LuweiZHANG HongWU ZhenhuaWang ZhenhuaWANG YiboLI HongyanMA XiaofeiXIE Yi
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.
