Inhibition by 6-hydroxydopamine of enhanced gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in spontaneously hypertensive rats.
The effects of chemical sympathectomy induced by 6-hydroxydopamine (6-OHDA) on the enhanced induction of gastric carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in spontaneously hypertensive rats (SHR), and the norepinephrine (NE) concentrations in their gastric wall and the labeling index of gastric epithelial cells were investigated. SHR rats and normotensive Wistar Kyoto rats (WKY) as controls were given MNNG (25 micrograms/ml) in their drinking water for 25 weeks and then i.p. injections of 6-OHDA (42 mg/kg twice within 24 hr, and then 105 mg/kg every 2 weeks from 1 week later). In control group (WKY rat + NaCl), gastric cancers were found in 2 (11%) of 18 rats examined in week 52. In SHR rats treated with NaCl solution only, the incidence of gastric cancers significantly increased, to 53% compared with that in control WKY rats. Treatment of SHR rats with 6-OHDA significantly decreased its incidence to 12% compared with the value in SHR rats treated with NaCl solution only. Prolonged administration of 6-OHDA to SHR rats significantly reduced the NE concentration in the antral portion of the gastric wall and the labeling index of antral epithelial cells. These findings indicate that prolonged i.p. treatment with 6-OHDA attenuated the normally higher incidence of MNNG-induced gastric cancer in SHR rats.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Iishi
H
H
Baba
M
M
Taniguchi
H
H
D000818:Animals; D004247:DNA / Q000096:biosynthesis; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000150:complications*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology; D011921:Rats, Inbred WKY; D013274:Stomach Neoplasms / Q000139:chemically induced*
D008769:Methylnitronitrosoguanidine; D016627:Oxidopamine; D004247:DNA; D009638:Norepinephrine