Genotoxicity of paraquat: micronuclei induced in bone marrow and peripheral blood are inhibited by melatonin

The ability of melatonin to influence paraquat-induced genotoxicity was tes ted using micronucleated polychromatic erythrocytes as an index of damage i n both bone marrow and peripheral blood cells of mice. Melatonin (10 mg/kg) or an equal volume of saline were administered intraperitoneally (ip) to m ice 30 min prior to an ip injection of paraquat (20 mg/kg x 2), and thereaf ter at 6-h intervals until the conclusion of the study (72 h). The number o f the micronucleated polychromatic erythrocytes increased after paraquat ad ministration both in peripheral blood and bone marrow cells. Melatonin admi nistration to paraquat-treated mice significantly reduced micronuclei forma tion in both peripheral blood and bone marrow cells; these differences were apparent at 24, 48 and 72 h after paraquat administration. The induction o f micronuclei was time-dependent with peak values occurring at 24 and 48 h. The reduction in paraquat-related genotoxicity by melatonin is likely due in part to the antioxidant activity of the indole. We did not observe effec ts of melatonin over paraquat in paraquat + melatonin groups incubated at 0 , 60 and 120 min. Mitomycin C, which was used as a positive control, also c aused the expected large rises in micronuclei in both bone marrow and perip heral blood cells at 24, 48 and 72 h after its administration. (C) 2000 Pub lished by Elsevier Science B.V. All rights reserved.