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Effect of Time and Duration of Exposure to 12-O-Tetradecanoylphorbol-13-acetate on X-Ray Transformation of C3H 10T Cells¹

Laboratory of Radiology, Department of Physiology, Harvard School of Public Health, Boston, Massachusetts 02115

We have confirmed our previous observations that the tumorpromoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) enhances transformation induced by low doses of X-rays. We report here that TPA exerts its effect primarily on actively proliferating cells and has little promoting effect once the cells have reached confluency. However, previously irradiated cells seeded at low density, allowed to reach confluency and then reseeded at low density maintain the capacity to respond to TPA treatment during this second round of proliferation.

These results indicate that: (a) as in vivo, TPA is effective even when treatment begins a long time after exposure to the initiating agent; (b) the enhancement of expression of X-ray transformation by TPA is not due to a simple stimulation of cell proliferation; (c) TPA enhancement does not result primarily from the conversion of premutational lesions in DNA to mutations; and (d) the promotional effects of TPA are probably not related to an effect on a DNA repair process.

¹ This research was supported by Grant CA-22704 awarded by the National Cancer Institute, Department of Health, Education and Welfare, and by Grant ES-00002 awarded by the National Institute of Environmental Health Sciences, Department of Health, Education and Welfare.

² To whom requests for reprints should be addressed.

Received 12/ 3/79. Accepted 2/27/80.