Post-treatment effects of DNA topoisomerase inhibitors on UVB- and X-ray-induced chromosomal aberration formations.
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.
Ishii
Y
Y
Department of Medical Genetics, B4, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita, Osaka, Japan. ishii@radbio.med.osaka-u.ac.jp
Ikushima
T
T
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002869:Chromosome Aberrations / Q000187:drug effects* / Q000528:radiation effects; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D054659:Diketopiperazines; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D009621:Nogalamycin / Q000494:pharmacology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D012303:Ring Chromosomes; D013997:Time Factors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014466:Ultraviolet Rays
D054659:Diketopiperazines; D019384:Nucleic Acid Synthesis Inhibitors; D010879:Piperazines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione; D009621:Nogalamycin