Radioprotective effects of the thiols GSH and WR-2721 against X-ray-induction of micronuclei in erythroblasts

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 (CSII) and S-2-/3-aminopropylamino/ethyl phosp horothioic acid (WR-2721), at a dose of 400 mg/kg body weight, and exposed to 6 Gy X-rays. GSH or WR-2721 was applied alone, or 60 and 30 min, respect ively, prior to X-ray-exposure. The number of MNPCEs was determined at 24 h after the thiol treatment and X-irradiation. The radioprotection and toxic ity caused in the mouse erythroblasts by GSH and WR-2721, as indicated by t he number of MNPCEs were dependent on the thiol applied. The stronger radio protective effect is obtained following WR-2721 administration than after G SH application. WR-2721 showed greater toxicity than GSH. The combination o f GSN and WR-2721 given before X-ray-exposure resulted in the most radiopro tective effect as compared to the respective single-drug treatment of mice. Application of the both thiols. without subsequent X-irradiation appeared to be the most toxic, compared with administration of WR-2721 or GSH alone. The effective radioprotection by the combined action of GSH and WR-2721 ag ainst genomic instability induced in the mouse erythroblasts by X-rays was shown. (C) 2000 Elsevier Science B.V. All rights reserved.