Tissue norepinephrine depletion as a mechanism for calcium chloride inhibition of gastric carcinogenesis in rats after treatment with N-methyl-N'-nitro-N-nitrosoguanidine and sodium chloride.
The effects of oral calcium chloride (CaCl2) on sodium chloride (NaCl)-enhanced induction of gastric carcinogenesis by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine, and the norepinephrine (NE) concentration in the gastric wall, were investigated in Wistar rats. Animals were given the carcinogen for 25 weeks and then chow pellets containing 10% NaCl with or without 8% or 4% CaCl2. In week 52, the incidence of gastric cancers, the NE concentration in the antral portion of gastric wall and the labelling index of antral epithelial cells were significantly greater in rats fed NaCl alone than in untreated control rats. Concomitant oral treatment with CaCl2 at 8%, but not 4%, significantly reduced the incidence of gastric cancers, the NE concentration in the antral portion of gastric wall and the labelling index of the antral epithelial cells in week 52 compared with those in rats fed NaCl alone. Because NE concentration reflects sympathetic nervous system activity, our findings suggest that the sympathetic nervous system could play a role in NaCl-enhanced gastric carcinogenesis. Our findings also suggest that NE depletion by CaCl2 may be related to its inhibition of NaCl-enhanced carcinogenesis.
Ishi
H
H
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Tatsuta
M
M
Baba
M
M
Yano
H
H
Uehara
H
H
Nakaizumi
A
A
D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008769:Methylnitronitrosoguanidine; D009638:Norepinephrine / Q000032:analysis*; D009955:Ornithine Decarboxylase / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000633:toxicity*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
D008769:Methylnitronitrosoguanidine; D012965:Sodium Chloride; D009955:Ornithine Decarboxylase; D002122:Calcium Chloride; D009638:Norepinephrine