Protection by oral phenylalanine against gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats

Abstract

Summary The effect of oral administration of L-phenylalanine on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in inbred Wistar rats. Oral administration of 6% phenylalanine after 25 weeks of treatment with the carcinogen significantly reduced the incidence and number of adenocarcinomas of the glandular stomach at experimental week 52. Oral administration of high dose phenylalanine significantly increased the basal serum gastrin level and significantly decreased the norepinephrine concentration in the antral portion of the gastric wall, as well as the labelling indices of antral mucosa. These findings indicate that orally administered phenylalanine inhibits the development of gastric cancers.Gastrointestinal regulatory peptides, such as vasoactive intestinal peptide (lishi et al., 1987), secretin (Howatson & Carter, 1987), cholecystokinin and its analogue (Satake et al., 1986), and gastrin (Tatsuta et al., 1977b), have been found to regulate development of cancers of the gastrointestinal tract and the pancreas. We recently found that prolonged alternate-day administration of the potent duodenal ulcerogen cysteamine after 25 weeks of N-methyl-N'-nitro-Nnitrosoguanidine (MNNG) treatment led to marked hypergastrinaemia and also to significant protection against the development of gastric cancers (Tatsuta et al., 1988a). These findings indicate that exogenous and endogenous gastrin may be closely associated with gastric carcinogenesis.Of all the gastrointestinal regulatory peptides, the antral hormone gastrin has been most extensively studied. Food plays an important role in the regulation of serum and tissue gastrin levels. Lichtenberger et al. (1982) reported that of the amino acids, L-phenylalanine (phenylalanine) has a strong stimulatory action on gastrin release. These findings suggest that phenylalanine should inhibit gastric carcinogenesis. Therefore, to test this possibility in the present work we examined the effect of oral administration of phenylalanine on the incidence, number, and histological appearance of adenocarcinomas in rats induced by MNNG. Materials and methods AnimalsYoung male Wistar rats (n = 60), aged about 6 weeks, were purchased from SLC, Japan (Shizuoka, Japan). The rats were housed in suspended wire-bottomed metal cages in animal quarters with controlled temperature (21-22°C), humidity (30-50%), and light (12-h cycle), and had free access to chow pellets (Oriental Yeast, Tokyo, Japan). Beginning with experimental week 26, the MNNG-treated rats were given normal tap water. They were divided into two groups, which were treated until the end of the experiment at week 52 as follows: group 1 (30 rats) were given regular laboratory chow pellets containing 1% phenylalanine ad libitum; group 2 (30 rats) received 6% phenylalanine orally. Phenylalanine (Sigma Chemical, St Louis, MO) was added to regular chow pellets and given ad libitum until the end of the experiment. The chow pellets, with or without added phenylalanine, w...

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.…”

Inhibition by galanin of experimental carcinogenesis induced by azaserine in rat pancreas

“…Dosage was determined on the basis of our previous results (Iishi et al, 1994. Injections were given s.c. in a volume of 1 ml/kg body weight between 2 and 3 p.m. at various sites.…”

Peptidergic innervation of human esophageal and cardiac carcinoma

“…In our previous investigations, we also observed many scattered nerve fibers in meningioma and cardiac cancer, which was closely related to tumor cells. In addition, accumulated data [5][6][7] show that neuropeptides are involved in the regulation of the growth of tumors. Considering these new advancements, we decided to study the distribution of neuropeptide-containing nerve fibers in esophageal and cardiac carcinomas as well as their relationship with tumors so as to find some new proofs about tumor innervation.…”