WR-2721: Inhibitor of cisplatin-induced micronuclei

The modulatory effect of S-2-/3-aminopropylamino/ethyl-phosphorothioic acid , (WR-2721, Amifostine) on induction of micronuclei by cis-diamminedichloro platinum[II] (CDDP) was studied. The adult, male Swiss mice were treated wi th WR-2721, at a hose of 200 mg/kg or 400 mg/kg body weight, and/or with CD DP, at a dose 5 mg/kg or 10 mg/kg body weight. WR-2721 was given alone or 3 0 min before CDDP administration. The frequency of micronucleated polychrom atic erythrocytes (MNPCEs) and also the number of polychromatic erythrocyte s (PCEs) in the bone marrow and peripheral blood, at 24 h after the drug ap plication, were determined. After administration of CDDP, the frequency of MNPCEs distinctly increased, and the number of PCEs decreased. As compared with the animals injected with CDDP only, in mice treated with WR-2721 befo re CDDP application, the number of MNPCEs was reduced and the frequency of PCEs was increased. However, WR-2721 given alone, without subsequent admini stration of cis-diamminedichloroplatinum[II], caused an increase in the num ber of micronucleated polychromatic erythrocytes and a decrease in the numb er of PCEs. The geno- and cyto-toxicity and chemoprotection were dependent on the doses of the agents WR-2721 and CDDP applied. In mice injected with CDDP and/or WR-2721, the patterns of changes in the frequency of MNPCEs and PCEs were similar in the bone marrow and peripheral blood, respectively. T he protective effect of the aminothiol compound WR-2721 against induction o f micronuclei and apoptotic cell death in the erythropoietic system by CDDP was shown. Teratogenesis Carcinog. Mutagen. 20:349-356, 2000 (C) 2000 Wile y-Liss, Inc.