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.