title: Effects of GSH and WR-2721 on induction of micronuclei by cyclophosphamide.
abstract: 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.
authors.affiliation: Department of Animal Physiology, Institute of Zoology, Jagiellonian University, Cracow, Poland. maz@zuk.iz.uj.edu.pl
authors.forename: L
authors.initials: L
authors.lastname: Mazur
authors.forename: A
authors.initials: A
authors.lastname: Bławat
mesh_terms: 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
chemical_list: D018906:Antineoplastic Agents, Alkylating; D005456:Fluorescent Dyes; D003520:Cyclophosphamide; D000165:Acridine Orange; D005978:Glutathione; D004999:Amifostine