Our aim is to obtain information on the frequency of oncogenic transformation as an explicit function of exposure time for a variety of dose rates on latent transformation damage remaining after protracted X-irradiation. This latent damage and its expression by the promoter 12-0-tetradecanoyl-phorbol-13-acetate will be investigated by chronic TPA-treatment of cells initiated with X-rays delivered at high dose rate or protracted over times up to 8 h. We will continue to use the C3H/10T1/2 cell line derived from mouse cells in which transformation is quantitated by scoring piled-up foci on top of a confluent monolayer. Experiments will be performed at 37 degrees C with actively growing cultures. We will continue to use a constant exposure time technique for cellular irradiation at reduced dose rates. At cumulative or acute doses of .25 to 4 Gy, we will assay the population of X-ray initiated cells by TPA-treatments at 0.1 Mug/ml beginning immediately after irratiation. The control groups (without TPA but with TAP-solvent) will follow the same procedure. Relative factors will be estimated from the ratio of the transformation frequencies from protracted exposures over time T to frequency from an acute exposure (4 Gy/min) to the same dose, with or without TPA versus (a) the dose to obtain information on the efficacy of rapair processes, or (b) the total exposure time to obtain information on the kinetics of repair processes.
