MELATONIN REDUCES PARAQUAT-INDUCED GENOTOXICITY IN MICE

The protection afforded by melatonin against paraquat-induced genotoxi city in both bone marrow and peripheral blood cells of mice was tested using micronuclei as an index of induced chromosomal damage. Melatoni n (2 mg/kg) or an equal volume of saline was injected i.p. into mice 3 0 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). Us ing fluorescence microscopy, the number of micronuclei in polychromati c erythrocytes (MN-PCE) per 2000 PCE (1000 PCE!slide) per mouse was co unted both in blood and bone marrow, and the ratio of PCE to normochro matic 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 th e PCE/NCE ratio. Melatonin inhibited the paraquat-induced increase in MN-PCE by more than 50% at 48 and 72h. Paraquat toxicity is believed t o be due to free radical generation. Since melatonin is known to be ai l efficient free radical scavenger, it is concluded that melatonin's p rotection against paraquat-induced genotoxicity is mediated, at least in part, by its free radical scavenging activity. (C) 1998 Elsevier Sc ience Ireland Ltd. All rights reserved.