Effect of X-ray dose protraction and a tumor promoter on transformation induction in vitro

We have investigated the effects of X-rays given in a brief exposure (1 min or less) or protracted over 5 h, on cell survival and the induction of neoplastic transformation in C3H/10T1/2 cells with an emphasis on latent transformation damage remaining after protracted irradiation. This latent damage and its expression were investigated at accumulated doses of 0.25 to 4 Gy by chronic treatment with TPA (12-O-tetradecanoyl-phorbol-13-acetate or phorbol myristate acetate) at 0.1 microgram/ml beginning after irradiation. Transformation incidence from protracted as well as brief X-irradiations was linearly related to X-ray dose in the presence of 0.1 microgram/ml TPA/ml. In the absence of TPA, the best fits were obtained with cubic rather than quadratic functions. The effect-modifying factors due to dose protraction were similar with or without TPA and averaged 4.6 at low doses (up to 2 Gy). Also within this dose range average transformation enhancement due to TPA was approximately 4. Our results indicate that dose protraction does not change the shape the dose-response curve for transformation, and that the shape change induced by TPA is also independent of dose protraction.