The protection afforded by melatonin against paraquat-induced genotoxicity in both bone marrow and peripheral blood cells of mice was tested using micronuclei as an index of induced chromosomal damage. Melatonin (2 mg/kg) or an equal volume of saline was injected i.p. into mice 30 min prior to the i.p. administration of paraquat (two injections of 15 mg/kg; the paraquat injections were given with a 24 h interval) and thereafter at 6 h intervals to the conclusion of the study (72 h). Using fluorescence microscopy, the number of micronuclei in polychromatic erythrocytes (MN-PCE) per 2000 PCE (1000 PCE/slide) per mouse was counted both in blood and bone marrow, and the ratio of PCE to normochromatic erythrocytes (NCE) (PCE/NCE) was calculated. Paraquat treatment increased the number of MN-PCE at 24, 48, and 72 h, both in peripheral blood and bone marrow cells, while no differences were observed in the PCE/NCE ratio. Melatonin inhibited the paraquat-induced increase in MN-PCE by more than 50% at 48 and 72h. Paraquat toxicity is believed to be due to free radical generation. Since melatonin is known to be an efficient free radical scavenger, it is concluded that melatonin's protection against paraquat-induced genotoxicity is mediated, at least in part, by its free radical scavenging activity.
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