ENHANCED TRANSFORMATION OF MOUSE 10T1/2 CELLS BY 12-O-TETRADECANOYLPHORBOL-13-ACETATE FOLLOWING EXPOSURE TO X-RAYS OR TO FISSION-SPECTRUM NEUTRONS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (2) , 477-483
Abstract
Addition of the tumor promoter 12-O-tetradecanolyphorbol-13-acetate (TPA) to C3H/10T1/2 cells [embryo fibroblast] after exposure to either X-rays or to fission-spectrum neutrons increases significantly the frequency of transformation without any effect on cell survival. Treatment of unirradiated cells with 0.1 .mu.g of TPA/ml alone results in a small increase in transformation frequency above background (i.e., from 1.1 .times. 10-5 to 1.0 .times. 10-4). Thus, besides being a promoter, TPA is also a weak initiator. Enhancement of radiation-induced transformation by TPA was relatively greater after low compared to high doses of either radiation. In addition, TPA causes the relative biological effectiveness of neutrons compared to X-rays to increase with increasing dose or with increasing frequency of transformation rather than to decrease, when TPA is not used. For X-ray doses from 0 .apprx. 120 rad, TPA raises transformation to frequencies approximately equal to those due to neutrons alone. Analysis of TPA enhancement in the context of the combined effect of 2 inducing agents, i.e., TPA plus a radiation, indicates that with either radiation TPA acts synergistically. Lastly, TPA altered the dependence of transformation frequency on the density of viable cells. As opposed to a constant frequency of transformants per surviving (or viable) cell, which was observed after a fixed dose of X-rays or neutrons for a range of cell inocula, the addition of TPA increased the frequency of transformation for all cell inocula (i.e., from .apprx. 20-6000 viable cells per 90-mm Petri dish). The frequency of transformation decreases with increasing size of the inoculum, a result interpreted to indicate the combined effect of an interference with cell-to-cell communication by TPA plus the fading of initiation events due to the radiation.