Preventive effect of melatonin against DNA damage induced by cyanide, kainate, glutathione/Fe3+/O2, or H2O2/Fe2+

We have investigated hydroxyl free radical ((OH)-O-.)-mediated damage to calf thymus DNA produced by potassium cyanide. kainate. H2O2/Fe2+, or glutathione/Fe3+ by in vitro method. When calf thymus DNA was exposed to potassium cyanide (0.5, 0.75, 1.0, 1.5, or 2.0 mM) or kainate (0.25. 0.5, or 1.0 mM) for 90 min at 37 degreesC in homogenate or the 9000g supernatant of mice brain, the quantity of DNA damage was observed to be concentration-dependent. Similarly, glutathione (1.0, 2.0, 4.0, 5.0, or 6.0 mM) inflicted damage on calf thymus DNA in the presence of Fe3+ (3.0 muM). In addition. hydrogen peroxide (0.15, 0.30, 0.75, 1.50, or 3.0 mM) also caused damage to calf thymus DNA in the presence of Fe2+ (3.0 muM) in the same manner. Furthermore, it was observed that the DNA damage induced by potassium cyanide (2.0 mM), kainate (0.5 mM), glutathione (4.0 mM)/Fe3+, and H2O2 (1.5 mM)/Fe2+ was prevented by the treatment with melatonin (1.0 or 1.5 mM), a potent (OH)-O-. scavenger. These results suggest that cyanide, kainate, glutathione/Fe3+, and H2O2/Fe2+-mediated (OH)-O-. may play a cardinal role for DNA damage induced by these chemicals. Hence the conclusion of the present study is that melatonin protects against DNA damage induced by the (OH)-O-. produced by these chemicals.