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

      Mutation Research

      Animals, Bone Marrow, drug effects, pathology, Chromosome Breakage, DNA, Erythroblasts, Herbicides, toxicity, Injections, Intraperitoneal, Male, Melatonin, metabolism, pharmacology, Mice, Micronuclei, Chromosome-Defective, Micronucleus Tests, Mitomycin, Mutagenicity Tests, Nucleic Acid Synthesis Inhibitors, Paraquat

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          The ability of melatonin to influence paraquat-induced genotoxicity was tested using micronucleated polychromatic erythrocytes as an index of damage in both bone marrow and peripheral blood cells of mice. Melatonin (10 mg/kg) or an equal volume of saline were administered intraperitoneally (ip) to mice 30 min prior to an ip injection of paraquat (20 mg/kgx2), and thereafter at 6-h intervals until the conclusion of the study (72 h). The number of the micronucleated polychromatic erythrocytes increased after paraquat administration both in peripheral blood and bone marrow cells. Melatonin administration to paraquat-treated mice significantly reduced micronuclei formation in both peripheral blood and bone marrow cells; these differences were apparent at 24, 48 and 72 h after paraquat administration. The induction of 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 effects 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 caused the expected large rises in micronuclei in both bone marrow and peripheral blood cells at 24, 48 and 72 h after its administration.

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