Suppression by iron chelator phenanthroline of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
The effect of prolonged administration of iron chelator phenanthroline on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine, and the labeling and apoptotic indices in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and intraperitoneal injections of phenanthroline at doses of 15 or 30 mg/kg body weight every other day. At week 52, feeding of sodium chloride significantly increased the incidence of gastric cancers, as compared with the control group. Prolonged injections of phenanthroline at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral supplementation with sodium chloride. Phenanthroline at both doses significantly decreased the labeling index of gastric cancers, which was enhanced by sodium chloride, and significantly increased the apoptotic index of gastric cancers, which was lowered by sodium chloride. In vitro examination using electron spin resonance revealed that sodium chloride promotes the production of hydroxyl radical during Fe(2+) oxidation by Fenton's reaction. These findings suggest that enhancement by sodium chloride of gastric carcinogenesis may be mediated by hydroxyl radicals.
Tatsuta
Masaharu
M
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, 3-3, Nakamichi 1-chome, Higashinari-ku, Osaka 537-8511, Japan.
Iishi
Hiroyasu
H
Baba
Miyako
M
Mikuni
Tomiko
T
Narahara
Hiroyuki
H
Uedo
Noriya
N
Yano
Hiroyuki
H
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003043:Cocarcinogenesis; D004357:Drug Synergism; D004578:Electron Spin Resonance Spectroscopy; D017665:Hydroxyl Radical / Q000633:toxicity*; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000627:therapeutic use*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000633:toxicity*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
D000951:Antigens, Neoplasm; D007502:Iron Chelating Agents; D010618:Phenanthrolines; D018809:Proliferating Cell Nuclear Antigen; D017673:Sodium Chloride, Dietary; D008769:Methylnitronitrosoguanidine; D017665:Hydroxyl Radical; C025205:1,10-phenanthroline