THE EFFECTS OF FARNESYLTRANSFERASE INHIBITOR L-744,832 AND RADIOTHERAPY ON H-RAS + (SVR A221A) CELL LINE.

Objective: We planned to assess the effects of two does farnesyltransferase ezymes inhibitor L-744,832, either alone or in combination with low, medium, and high dose radiation on cultured H-Ras positive cells (SVR A221a) regarding the cell count, DNA indices and apoptosis determined by flow-cytometric method. Material and Method: H-Ras positive (H-Ras +) cells were incubated. At the 3rd hour of the incubation, L-744,832 is added to study groups in following amounts. On the 3rd day of incubation, 2, 6 and 10 gray doses radiation was applied. After incubation period, study and control groups were evaluated for cell numbers, cell cycle and apoptosis percentage. Results: Total count of H-Ras positive cells were significantly lower in all study groups compared with the control group, this finding was more prominent in RT2+L2, RT3, RT3+L1, and RT3+L2 groups. Apoptosis ratios were found to be similar to the control group in L1, L2, and RT1 groups, while it was significantly and similarly higher in other groups. Expect L1, the ratio of the cells in G2/M phase was significantly higher compared to the control group. The most prominent increase was observed in RT3, RT3+L1, and RT3+L2 groups. Conclusion: Possible curative effects of this agent on ras oncogene related neoplastic disease may lead to new treatment protocols including L-744,832 alone or in combination with radiotherapy. [ABSTRACT FROM AUTHOR]