Effect of tumor promoters, protease inhibitors, and repair processes on x-ray-induced sister chromatid exchanges in mouse cells.
The induction of sister chromatid exchanges (SCE) in the second postirradiation mitosis was studied in mouse 10T1/2 cells irradiated with 400 rads (4 grays) and maintained in stationary growth for several hours 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 hr; SCE declined with longer recovery intervals. The influence of postirradiation incubation with the tumor promoter 12-O-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 hr) SCE. TPA (0.1 microgram/ml and 1.0 microgram/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. These results are discussed in relation to the hypothesis that promotional events in carcinogenesis may involve the expression of mutational damage in cells by mitotic segregation.
D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects / Q000528:radiation effects*; D004260:DNA Repair; D051379:Mice; D010704:Phorbols / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010704:Phorbols; D011480:Protease Inhibitors; D013755:Tetradecanoylphorbol Acetate