Objective: The purpose of this study was to measure and compare the effect of d-alpha-tocopheryl succinate (alpha-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 (OVGI and SKOV3) were treated with alpha-TS (37.6 microM) 20 hours before 100 cGy gamma-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 alpha-TS. cells were incubated in the presence of alpha-TS (18.8 and 37.6 microM) for 24 hours, and alpha-TS was extracted with hexane using a-tocopheryl acetate as an internal standard. The levels of alpha-TS were determined by HPLC.
Results: Results showed that alpha-TS induced chromosomal damage in both human cervical cancer cells and ovarian cancer cells, but not in human normal fibroblasts in culture. In addition, alpha-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 alpha-TS, suggesting that increased sensitivity of cancer cells to alpha-TS is acquired during transformation.
Conclusion: The use of alpha-TS during radiation therapy may improve the efficacy of radiation therapy by enhancing tumor response and decreasing some of the toxicities on normal cells.