Radiation In Human Carcinoma Cells Research Articles

Ultraviolet radiation down-regulates expression of the cell-cycle inhibitor p21WAF1/CIP1 in human cancer cells independently of p53

Purpose : To investigate the regulation of G1 cyclin-dependent kinase inhibitor p21WAF1/CIP1 by ultraviolet (UV) radiation in human carcinoma cells. Materials and methods : Human cancer cell lines were irradiated with UV-C (254nm) radiation, and their responses were characterized by Western blotting, Northern blotting, semi-quantitative RT-PCR analysis, trypan blue staining and flow cytometric cell cycle analysis. Results : At 24 h after UV irradiation, p21 expression was downregulated in various cancer cell types (breast, prostrate, cervix, colon, glioma, squamous cancers), independently of their p53 genetic and functional status. UV-mediated down-regulation of p21 was dose- and time-dependent, was observed at the protein and mRNA levels, and did not correlate with cytotoxicity. Reduction of p21 protein levels required about 4 and 1 h, respectively, in MCF-7 and MDA-MB-231 breast cancer cells; some of the UV-induced decreases in p21 levels in these cell lines was due to enhanced proteasomal degradation. Despite decreased p21 levels, UV-irradiated breast cancer cells with wildtype p53 (MCF-7) retained the capacity for G1 cell-cycle arrest, whereas UV-treated cells with mutant p53 (MDA-MB-231) accumulated in S phase, suggesting a p53-dependent G1 checkpoint in MCF-7. UV treatment caused other alterations in cellcycle regulatory, DNA repair and tumour suppressor genes, as described in this report. Conclusions : In contrast to X-rays, UV causes down-regulation of the cell-cycle inhibitor p21 in tumour cells. It is postulated that this may be an adaptation to promote the growth and survival of transformed cells.

Synergistic cytotoxic effects of ether phospholipid analogues and ionizing radiation in human carcinoma cells

Background and purpose: There is growing evidence in recent years that the antiproliferative effects of ionizing radiation may not be exclusively mediated via DNA damage but also by interactions and alterations of cell membrane associated processes. Here, we tested the hypothesis that membrane active cytotoxic ether lipids and analogues may interact with ionizing radiation, enhancing its antiproliferative effects. Materials and methods: The two epithelial tumor cell lines HTB 43 and KB, and the ether lipid resistant subline KBr were treated by a combination of radiation and ether lipids. Cytotoxic effects were measured by colony forming assays and the effects on membrane phospholipids were determined by quantitative thin-layer chromatography of cell lipid extracts. Results: We present evidence that some ether lipids show supra-additive cytotoxic effects with ionizing radiation. These effects seem to depend on the same structural properties of ether lipids that determine their intrinsic cytostatic and cytotoxic activity. Identical growth inhibitory results were achieved when cells were treated before, or 30 min after irradiation. Analysis of major membrane phospholipids revealed no statistically significant differences of phospholipid distribution pattern in cells exposed to both treatment modalities. Conclusion: Our data indicate that changes of overall membrane phospholipid composition do not seem to be the mechanism of synergistic antiproliferative activity of ether lipids and ionizing radiation.