Preventive effect of melatonin against DNA damage induced by cyanide, kainate, glutathione/Fe(3+)/O(2), or H(2)O(2)/Fe(2+).
We have investigated hydroxyl free radical (.OH)-mediated damage to calf thymus DNA produced by potassium cyanide, kainate, H(2)O(2)/Fe(2+), or glutathione/Fe(3+) 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 degrees C 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 Fe(3+) (3.0 microM). 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 Fe(2+) (3.0 microM) 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)/Fe(3+), and H(2)O(2) (1.5 mM)/Fe(2+) was prevented by the treatment with melatonin (1.0 or 1.5 mM), a potent .OH scavenger. These results suggest that cyanide, kainate, glutathione/Fe(3+), and H(2)O(2)/Fe(2+)-mediated .OH 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 produced by these chemicals.
Yamamoto
H A
HA
University of Tsukuba, Institute of Community Medicine, Tsukuba, Ibaraki 305-8575, Japan. hiro_aki@d4.dion.ne.jp
Mohanan
P V
PV
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011190:Potassium Cyanide / Q000494:pharmacology*
D017665:Hydroxyl Radical; D004247:DNA; D006861:Hydrogen Peroxide; D007501:Iron; D005978:Glutathione; D008550:Melatonin; D011190:Potassium Cyanide; D007608:Kainic Acid