Bimodal induction of sister-chromatid exchanges by luminol, an inhibitor of poly(ADP-ribose) synthetase, during the S-phase of the cell cycle.
The cell cycle dependence of sister chromatid exchanges (SCEs) induced by luminol, a new potent inhibitor of poly(ADP-ribose) synthetase, was studied in Chinese hamster V79 cells. Continuous treatment with luminol during two whole cell cycles in the presence of 5-bromo-2'-deoxyuridine (BrdUrd), or in the first or second cycle induced SCEs very efficiently in a linear dose-dependent manner. However, no enhancement of SCE levels was observed after luminol treatment in a cycle preceding BrdUrd treatment, in contrast to results found with other strong SCE inducers such as cis-diammine-dichloroplatinum (II) (CDDP) and mitomycin C (MMC). Luminol was about ten times as effective in inducing SCEs as 3-aminobenzamide (3AB)', an inhibitor of the NAD+ site of poly(ADP-ribose) synthetase. The induction of SCEs by luminol was restricted to the S-phase of the cell cycle with peaks at an early and a late stage, corresponding to the biphasic replication of DNA. The mechanism of SCE appears to be the same at the early and late stages of S-phase for luminol-induced SCE formation.
Ikushima
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Research Reactor Institute, Kyoto University, Osaka, Japan.
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA; D004261:DNA Replication; D007700:Kinetics; D008165:Luminol / Q000494:pharmacology*; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016196:S Phase; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D008937:Mitomycins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016685:Mitomycin; D008165:Luminol; D004247:DNA; D001973:Bromodeoxyuridine; D002945:Cisplatin