nogalamycin and Chromosome-Deletion

Post-treatments with nogalamycin, an inhibitor of DNA topoisomerase I, for last 3h of the culture (during the G2 phase) drastically enhanced the yield of ultraviolet light B (UVB)-induced exchange-type chromatid aberrations, while showing little effect on the formation of breakage-type aberrations in Chinese hamster V79 cells. These results are very similar to those obtained with ICRF-193, an inhibitor of topoisomerase II, with respect to the effect on UVB-induced chromatid aberrations. Thus, both types of topoisomerases may suppress the formation of exchange-type chromatid aberrations in the G2 phase which is suggested to be the principal stage of the cell cycle for chromatid aberration formation.In human lymphocytes irradiated with X-rays before phytohaemagglutinin (PHA) stimulation, post-treatments with nogalamycin through the whole cell cycle enhanced only the yield of dicentrics, while showing little effect on the yields of any other chromosome-type aberrations. Nogalamycin added 6h after PHA stimulation to irradiated cells also showed almost the same effects, whereas, addition of nogalamycin 24h after PHA stimulation showed no effect on X-ray-induced chromosome-type aberrations. These results suggest that X-ray-induced DNA damage lead to chromosome-type aberrations before the start of S phase and topoisomerase I may suppress the formation of dicentrics, exchange-type chromosome aberrations. Post-treatments with ICRF-193 showed no effect on the formation of X-ray-induced chromosome-type aberrations, suggesting nonparticipation of topoisomerase II in this process.

Topics: Animals; Cell Cycle; Cell Line; Chromosome Aberrations; Chromosome Breakage; Chromosome Deletion; Diketopiperazines; Humans; Lymphocytes; Male; Nogalamycin; Nucleic Acid Synthesis Inhibitors; Piperazines; Ring Chromosomes; Time Factors; Topoisomerase I Inhibitors; Topoisomerase II Inhibitors; Ultraviolet Rays