D-Alpha-Tocopheryl Succinate (Vitamin E) Enhances Radiation-Induced Chromosomal Damage Levels in Human Cancer Cells, but Reduces it in Normal Cells
2002
Kumar, Bipin | Jha, Mitra N. | Cole, W. C. (William C) | Bedford, Joel S. | Prasad, Kedar N.
Objective: The purpose of this study was to measure and compare the effect of d-α-tocopheryl succinate (α-TS) in modifying radiation-induced chromosomal damage in human normal cells and cancer cells in culture. Methods: Three human normal fibroblast cell lines (GM2149, AG1522 and HF19) and three human cancer cell lines, cervical cancer (HeLa) and ovarian carcinoma cells (OVG1 and SKOV3) were treated with α-TS (37.6 μM) 20 hours before 100 cGy γ-irradiation. After 30 minutes of irradiation, colcemid was added and cells were fixed. One hundred randomly selected metaphase cells were scored for the presence of chromatid gaps and breaks. To study the cellular accumulation of α-TS, cells were incubated in the presence of α-TS (18.8 and 37.6 μM) for 24 hours, and α-TS was extracted with hexane using α-tocopheryl acetate as an internal standard. The levels of α-TS were determined by HPLC. Results: Results showed that α-TS induced chromosomal damage in both human cervical cancer cells and ovarian cancer cells, but not in human normal fibroblasts in culture. In addition, α-TS enhanced the level of radiation-induced chromosomal damage in cancer cells, but it protected normal cells against such damage. Both cancer cells and normal cells accumulated similar levels of α-TS, suggesting that increased sensitivity of cancer cells to α-TS is acquired during transformation. Conclusion: The use of α-TS during radiation therapy may improve the efficacy of radiation therapy by enhancing tumor response and decreasing some of the toxicities on normal cells.
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