Effect of melatonin on mitotic and proliferation indices, and sister chromatid exchange in human blood lymphocytes

Cells from human peripheral blood were cultured in vitro in the presence of 0.05 to 1.00 mM melatonin, 10(-7) M mitomycin C (positive control) and 0.5% ethanol (solvent control) for 72 h at 37 +/- 1 degrees C. Lymphocytes were examined for mitotic and proliferation indices, and for the incidence of sister chromatid exchange. The results indicate that the lymphocytes which were cultured in the presence of greater than or equal to 0.20 mM concentrations of melatonin exhibited a significant and concentration-dependent decrease in mitotic index and alteration in proliferation kinetics. This was demonstrated by an increase in the frequency of lymphocytes in their first division, with a concomitant decrease in the second and third or later division cells. The incidence of sister chromatid exchange was similar in the lymphocytes exposed to 0.05 to 1.00 mM melatonin and untreated controls. Exposure of the cells to ethanol, the solvent used, did not alter either the mitotic or proliferation indices, or the frequency of sister chromatid exchange. The lymphocytes treated with mitomycin C showed the expected decrease in mitotic and proliferation indices, and an increased incidence of sister chromatid exchange. These observations indicate that melatonin, when continuously present in the cultures for 72 h at the concentrations tested, while not genotoxic as indicated by the sister chromatid exchange assay, inhibits the proliferation of mitogen stimulated (and proliferating) human blood lymphocytes at supraphysiological concentrations.