Effect of TPA, Okadaic Acid and 1α,25-dihydroxyvitamin D₃ on Neoplastic Transformation Induced by ⁶⁰Co Gamma-rays or ²⁵²Cf Fission Neutrons in Balb/c 3T3 Cells

Abstract

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), 1α,25-dihydroxyvitamin D₃ [1α,25(OH)₂D₃] and okadaic acid were individually examined on the neoplastic transformation of Balb/c 3T3 cells which were exposed to either ⁶⁰Co gamma-rays or ²⁵²Cf fission neutrons. The addition of 1α,25(OH)₂D₃, or TPA, enhanced the transformation induced by gamma-rays or low doses of fission neutrons. No enhancement was observed by the addition of okadaic acid except at toxic concentrations (5 ng/ml) and with higher doses of radiation. Moreover, the enhancement of transformation by either 1α,25(OH)₂D₃ or TPA decreased as the radiation dose was increased. The enhancement ratio, calculated by least-square analysis from 0 Gy to 1 Gy, was greater for 1α,25(OH)₂D₃ than for TPA, and also greater for gamma-ray irradiation than for neutron irradiation. These results suggest that the promotion of radiation-induced transformation depends on the level of the initial damage caused by radiation, and that the differences in the enhancement properties of different chemicals may be due to different individual triggering mechanisms involved in the transformation process.