ONCOGENIC TRANSFORMATION THROUGH THE CELL-CYCLE AND THE LET DEPENDENTINVERSE DOSE-RATE EFFECT

Synchronised populations of mouse C3H/10T-1/2 cells were obtained by a stringent mitotic dislodgment procedure. Mitotic cells rapidly attach and progress sequentially through the cell cycle. Irradiation (3 Gy o f X rays) was carried out at intervals from 0 to 18 h after initiating cell cycle progression of the mitotic cells. Oncogenic transformation was enhanced 10-fold over cells irradiated soon after replating (G1 a nd S phases) for cells in a near 2 h period corresponding to cells in G2 phase but not in mitosis. The cell surviving fraction had a 2-1/2-f old variation with resistant peaks corresponding to the late G1 and la te S phases. These findings provide experimental support for the hypot hesis initiated by Rossi and Kellerer and developed by Brenner and Hal l to explain the LET dependent inverse dose rate effect for oncogenic transformation.