Effects of GSH and WR-2721 on induction of micronuclei by cyclophosphamide.
The frequency of micronucleated polychromatic erythrocytes (MNPCEs) was assessed in the bone marrow and peripheral blood of adult male Swiss mice treated with reduced glutathione (GSH) and/or S-2-/3-aminopropylamino/ethyl phosphorothioic acid (WR-2721), at a dose of 400 mg/kg body weight, and/or with 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. The number of MNPCEs was determined at 24 h after the drug application. After treatment of mice with CP, the frequency of MNPCEs was distinctly increased. 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 cytotoxic and chemoprotective effects, compared with the respective single-thiol treatment of mice. The most effective protection against CP-induced genotoxicity was observed in the case of treatment of mice with WR-2721and GSH, respectively, 30 and 15 min before CP administration. The most cytotoxic effect of the thiols was found when GSH given 30 min prior to WR-2721 application. 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.
Mazur
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Department of Animal Physiology, Institute of Zoology, Jagiellonian University, Cracow, Poland. maz@zuk.iz.uj.edu.pl
Bławat
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D000165:Acridine Orange; D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects; D003520:Cyclophosphamide / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004357:Drug Synergism; D004912:Erythrocytes / Q000187:drug effects; D005456:Fluorescent Dyes; D005978:Glutathione / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015162:Micronucleus Tests
D018906:Antineoplastic Agents, Alkylating; D005456:Fluorescent Dyes; D003520:Cyclophosphamide; D000165:Acridine Orange; D005978:Glutathione; D004999:Amifostine