Promotion by Nialamide of Gastric Carcinogenesis Induced by N‐Methyl‐N′‐nitro‐N‐nitrosoguanidine in Wistar Rats

Abstract

The effects of nialamide, a monoamine oxidase inhibitor, on the incidence, number, and histology of gastric cancers induced by N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG) were investigated in male Wistar rats. Rats were given subcutaneously 50 mg/kg body weight of nialamide in depot form every other day after 25 weeks of oral treatment with MNNG. Prolonged alternate‐day administration of nialamide caused a significant increase in the incidence and number of gastric cancers of the glandular stomach in week 52, However, it did not affect the histology of the cancers. Nialamide also caused a significant increase in tissue norepinephrine concentrations in the gastric wall and in the labeling indices of the gastric mucosae. However, nialamide had no influence on serum gastrin levels in the fasting state and after re‐feeding. These findings indicate that nialamide promotes gastric carcinogenesis and that this may be related to its effects in increasing norepinephrine in the gastric wall and stimulating proliferation of gastric epithelial cells.

Is norepinephrine an etiological factor in some types of cancer?

“…9 I now describe in greater detail the aforementioned 7 lines of evidence that support an etiological role for NE in some types of cancer. The first line of evidence has been put forth primarily by a group of researchers in Japan during the last several decades, [11][12][13][14][15][16][17][18][19][20] as well as by some Russian scientists [21][22][23] and others. 24,25 This line indicates that in rodents the level of NE, or degree of activation of adrenoceptors with drugs, in certain bodily tissues correlates with the degree of tumorigenesis in those tissues.…”

“…24,25 This line indicates that in rodents the level of NE, or degree of activation of adrenoceptors with drugs, in certain bodily tissues correlates with the degree of tumorigenesis in those tissues. In particular, during chemically induced carcinogenesis, when the level of NE is increased with drugs such as bombesin 11,12 or the tricyclic antidepressant desipramine, 13 or a low protein diet, 14,15 tumorigenesis increases; when the level of NE is decreased with 6-hydroxydopamine, 16 phenylalanine, 17 or cysteamine, 18,19 tumorigenesis decreases. However, when the level of NE is decreased with clonidine, tumorigenesis is unaffected.…”

“…20 These studies focused on the gastrointestinal (GI) tract, but also studied other organ system components such as the liver. 18 In most of these studies, tumorigenesis was induced by the carcinogens N-methyl-N 0 -nitro-N-nitrosoguanidine 11,14,17,20 and azoxymethane, 12,13,15,16,19 which increase the baseline number of tumors, and the various drug and other treatments were tested for modulation of this baseline number. Testing for modulation of tumorigenesis without using chemical carcinogens is not feasible due to the extremely large sample size of animals that would be necessary since the number of tumors would be quite low.…”

Induction by bombesin of peritoneal metastasis of gastric cancers induced by N -methyl- N ?-nitro- N -nitrosoguanidine in Wistar rats

“…In another study, we found that long-term administration of bombesin after MNNG treatment significantly increased the incidence of gastric cancers induced by MNNG [8]. However, in a gastric cancer model, peritoneal metastasis from the gastric cancers was observed in only one (7%) of 15 tumor-bearing rats (data not shown).…”

“…Bombesin has important roles in the physiology and pathology of the gastrointestinal system [5][6][7]. Previously, we [8] found that bombesin enhanced gastric carcinogenesis in Wistar rats after the administration of N-methyl-NЈ-nitro-N-nitrosoguanidine (MNNG) was stopped. These findings suggested that bombesin might induce the development of peritoneal metastasis from gastric cancers.…”