ASSESSMENT OF MICRONUCLEUS INDUCTION IN SCCVII CELLS TREATED WITH BIOREDUCTIVE AGENTS, WIN-59075 (SR-4233) AND MITOMYCIN-C, UNDER AEROBIC AND HYPOXIC CONDITIONS

WIN 59075 (SR4233, tirapazamine) is a promising bioreductive antitumor agent preferentially more toxic to hypoxic cells and presently underg oing phase I clinical trials. In this investigation, we have examined the applicability of the cytokinesis-block micronucleus assay to asses s the effects of bioreductive agents. SCCVII tumor cells were treated with WIN 59075 or mitomycin C at various concentrations under aerobic and hypoxic conditions. Significant induction of micronuclei in binucl eate cells was demonstrated in a dose-dependent fashion and it appeare d to be strongly correlated with the loss of clonogenicity in the colo ny assay. Both agents showed selectively higher toxicity to hypoxic ce lls than to aerobic cells and the ratios of the concentrations require d to obtain the equivalent effects under aerobic and hypoxic condition s could be also estimated by this method as follows: the hypoxic toxic ity ratios were 120-130 for WIN 59075 and 3.0-3.3 for mitomycin C. For several favorable characteristics, the cytokinesis-block micronucleus assay can provide an alternative, rapid, and reproducible means for e valuation of antitumor activities from chromosomal breakage caused by the bioreductive agents.