Ortiz G G, Reiter R J, Zúñiga G, Melchiorri D, Sewerynek E, Pablos M I, Oh C S, García J J, Bitzer-Quintero O K
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, USA.
Mutat Res. 2000 Jan 24;464(2):239-45. doi: 10.1016/s1383-5718(99)00197-7.
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.
以小鼠骨髓和外周血细胞中微核多染红细胞作为损伤指标，检测褪黑素对百草枯诱导的遗传毒性的影响。在腹腔注射百草枯（20mg/kg×2）前30分钟，给小鼠腹腔注射褪黑素（10mg/kg）或等体积的生理盐水，之后每隔6小时注射一次，直至研究结束（72小时）。百草枯给药后，外周血和骨髓细胞中的微核多染红细胞数量均增加。给百草枯处理的小鼠注射褪黑素可显著减少外周血和骨髓细胞中的微核形成；这些差异在百草枯给药后24、48和72小时明显。微核的诱导呈时间依赖性，峰值出现在24和48小时。褪黑素降低百草枯相关的遗传毒性可能部分归因于吲哚的抗氧化活性。在0、60和120分钟孵育的百草枯+褪黑素组中，我们未观察到褪黑素对百草枯的影响。作为阳性对照的丝裂霉素C在给药后24、48和72小时也导致骨髓和外周血细胞中的微核预期大幅增加。
