Effect of tumor promoters, protease inhibitors, and repair processes on x-ray-induced sister chromatid exchanges in mouse cells.

Abstract

The induction of sister chromatid exchanges (SCE) in the 2nd post-irradiation mitosis was studied in mouse 10T1/2 cells irradiated with 400 rads (4 grays) and maintained in stationary growth for several h after X-ray exposure (similar to liquid holding recovery experiments in bacterial cells). X-irradiation with no recovery period induced few SCE. With short recovery intervals, however, the SCE frequency rose in parallel with the increase in survival, reaching a maximum increase of 2-fold after 4 h; SCE declined with longer recovery intervals. The influence of post-irradiation incubation with the tumor promoter 12-0-tetradecanoylphorbol 13-acetate (TPA) and with the protease inhibitors antipain and leupeptin was studied on spontaneous, X-ray-induced (no recovery), and recovery-induced (4 h) SCE. TPA (0.1 .mu.g/ml and 1.0 .mu.g/ml) increased the frequency of both spontaneous and direct X-ray-induced SCE, but not of recovery-induced SCE. Incubation with the protease inhibitors suppressed both TPA- and recovery-induced SCE, but had no effect on direct X-ray-induced SCE. Promotional events in carcinogenesis may involve the expression of mutational damage in cells by mitotic segregation.