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Induction of micronucleated erythrocytes by MEA, AET, WR-2721 and X-rays
1Department of Animal Physiology, Jagiellonian University, Cracow, Poland.
Abstract:
The induction of micronucleated polychromatic erythrocytes (MNPCEs) was assessed in the bone marrow of adult male Swiss mice treated with MEA (cysteamine HCl), AET (2-aminoethylisothiouronium Br.HBr), or WR-2721 (S-2-(3-aminopropylamino)ethyl phosphorothioic acid), at a dose of 200 mg/kg body weight, and/or exposed to 6 Gy X-rays. MEA, AET, or WR-2721 was given alone or 15 min prior to X-ray exposure, and the frequency of MNPCEs was determined 24 h after the aminothiol treatment and X-irradiation of mice. A genotoxic effect was shown for MEA, AET, WR-2721, and X-rays, as well as a protective effect of the aminothiols against X-ray-induced genotoxicity in the mouse erythropoietic system. The aminothiol drugs given alone, without subsequent X-irradiation, elevated the frequency of MNPCEs, and WR-2721 appeared to be less toxic than AET and MEA. After exposure of mice to X-rays, the number of MNPCEs was distinctly increased. MEA, AET, or WR-2721 administration prior to X-irradiation resulted in a reduction of the X-ray-induced elevation of the frequency of micronuclei, but a stronger radioprotective effect was obtained following WR-2721 and AET treatment than after MEA application. So, the genotoxic and radioprotective effect of the aminothiols was dependent on the compound applied.
Insights
Aminothiols like MEA, AET, and WR-2721 showed genotoxicity and radioprotective effects against X-ray damage in mice. The protective efficacy varied among compounds, with WR-2721 and AET being more effective than MEA.
Area of Science:
- Toxicology
- Radiation Biology
- Genetics
Background:
- Aminothiols are investigated for radioprotective properties.
- X-rays induce genotoxicity, evidenced by micronuclei formation.
- The erythropoietic system is a target for genotoxic and radioprotective agents.
Purpose of the Study:
- To assess the genotoxic and radioprotective effects of MEA, AET, and WR-2721.
- To compare the efficacy of different aminothiols in mitigating X-ray-induced genotoxicity.
- To evaluate the impact of these compounds on micronucleated polychromatic erythrocytes (MNPCEs) in mice.
Main Methods:
- Adult male Swiss mice were treated with MEA, AET, or WR-2721 (200 mg/kg) alone or before 6 Gy X-ray exposure.
- The frequency of MNPCEs in bone marrow was determined 24 hours post-treatment.
- Statistical analysis was performed to compare treatment groups.
Main Results:
- MEA, AET, WR-2721, and X-rays individually demonstrated genotoxic effects.
- Aminothiols alone increased MNPCE frequency, with WR-2721 showing lower toxicity than AET and MEA.
- Pre-treatment with aminothiols reduced X-ray-induced MNPCEs, with WR-2721 and AET providing stronger protection than MEA.
Conclusions:
- The tested aminothiols exhibit both genotoxic and radioprotective properties.
- The genotoxic and radioprotective effects are compound-dependent.
- WR-2721 and AET show greater potential as radioprotectors compared to MEA in this model.
