Effects of GSH and WR-2721 on induction of micronuclei by cyclophosphamide

The frequency of micronucleated polychromatic erythrocytes (MNPCEs) was ass essed in the bone marrow and peripheral blood of adult male Swiss mice trea ted with reduced glutathione (GSH) and/or S-2-/3-aminopropylamino/ethyl pho sphorothioic acid (WR-2721), at a dose of 400 mg/kg body weight, and/or wit h cyclophosphamide (CP), at a dose of 200 mg/kg body weight. GSH was given 60 or 15 min and/or WR-2721 was applied 30 min before CP administration. Th e number of MNPCEs was determined at 24 h after the drug application. After treatment of mice with CP, the frequency of MNPCEs was distinctly increase d. The stronger chemoprotective effect against CP-induced cytotoxicity was obtained following GSH administration than after WR-2721 injection. WR-2721 characterized greater cytotoxicity than GSH. The combination of GSH and WR -2721 given alone, or before CP administration resulted in the most cytotox ic and chemoprotective effects, compared with the respective single-thiol t reatment of mice. The most effective protection against CP-induced genotoxi city was observed in the case of treatment of mice with WR-2721 and GSH, re spectively, 30 and 15 min before CP administration. The most cytotoxic effe ct of the thiols was found when GSH given 30 min prior to WR-2721 applicati on. The chemoprotection and cytotoxicity caused in the mouse erythroblasts by GSH and WR-2721, as indicated by the number of MNPCEs were dependent on the thiol(s) given, and the time intervals between the drug administration. The modulatory effect of the thiols GSH and WR-2721 on 'delayed apoptosis' induced in the erythropoietic system by cyclophosphamide was shown. (C) 19 99 Elsevier Science Ireland Ltd. All rights reserved.