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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphological and biochemical changes reflecting the process of genesis of experimental stomach cancer were studied and compared in experiments carried out on 170 rats to whom N-methyl-N'-nitro-N-nitrosoguanidine had been given in drinking water. The concentration of the compound in drinking water was 167 mg/l. Malignization mostly developed during the ingrowth of the epithelial complexes involved in the process of carcinogenesis into the submucous membrane, in rare cases, into the mucous membrane itself. The results of experiments showed that biochemical changes preceded morphological alterations. The signs of inhibition of the synthesis of the isoenzyme spectrum of pepsinogen-pepsin revealed the qualitative changes of biochemical processes of the epithelium. A possible dependence of morphological features of the process of carcinogenesis on the evolutionally-established functional peculiarities of rat stomach epithelium is discussed.
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PMID:Morphological and biochemical changes induced in rat stomach by N-methyl-N'-nitro-N-nitrosoguanidine. 47 27

Changes in the isozymes of pepsinogen (Pg) separated from the glandular stomachs of rats were studied by polyacrylamide gel electrophoresis during carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), from the beginning of MNNG administration to 3 months after the end of its 7-month regimen. In 13 of 25 rats killed successively, one (Pg 1) of the three pepsinogen isozymes (Pg 1, 3, 4) normally present in the pyloric mucosa had decreased or disappeared. It decreas was observed from 1 week after the beginning of MNNG treatment to at least 3 months after the end of the 7-month MNNG administration. Remarkable histopathologic changes were found from 8 months after MNNG was given, and rats showing such unusual histopathologic alterations also had changes in their pepsinogen isozyme pattern. In 4 of 27 rats, two (Pg 1, 2) of the four isozymes of pepsinogen (Pg 1-4) in the fundic mucosa decreased or disappeared from 3 months after the beginning of MNNG treatment to at least 2 months after the end of its 7-month administration. Histopathologic changes induced by MNNG were not as remarkable in the fundic mucosa as in the pyloric mucosa.
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PMID:Changes in pepsinogen isozymes in stomach carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine. 118 10

In children and adolescents from two areas of Costa Rica with contrasting gastric cancer risks, two factors suspected to be linked to the natural history of the disease were tested: serum antibodies to Helicobacter pylori and serum pepsinogen levels. One hundred fifty-five subjects from the high-risk area of Turrubares were compared to 127 from the low-risk area of Hojancha. No significant differences were found in the prevalence of IgG or IgA antibodies to Helicobacter pylori between the two regions. The prevalence of IgG was 65.8% in the high-risk area and 72.4 in the low-risk area, and that of IgA was 43% in both areas. The levels of pepsinogen, especially pepsinogen C, were significantly elevated in subjects with H. pylori antibodies in their serum. The mean levels of pepsinogen C in those negative, positive, and strong positive for H. pylori antibodies were 8.7, 14.3, and 21.1 ng/ml. These findings suggest that H. pylori-associated gastritis, predominantly of antral localization, is very prevalent in Costa Rican children and adolescents. Such gastritis might be associated with a high prevalence of intestinal metaplasia and a high gastric cancer risk in the inland, but not the coastal rural populations. H. pylori may therefore be an insufficient cause whose role in gastric carcinogenesis is contingent upon the presence of other factors.
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PMID:Antibodies to Helicobacter pylori and pepsinogen levels in children from Costa Rica: comparison of two areas with different risks for stomach cancer. 130 56

Considerable knowledge has recently accumulated on the mechanism by which Helicobacter pylori (H. pylori) induces chronic gastritis. Although H. pylori is not an invasive bacterium, soluble surface constituents can provoke pepsinogen release from gastric chief cells or trigger local inflammation in the underlying tissue. Urease appears to be one of the prime chemoattractants for recruitment and activation of inflammatory cells. Release of cytokines, such as tumor necrosis factor alpha, interleukin 1 and 6, and oxygen radicals, leads to a further tissue inflammation accompanied by a potent systemic IgA and IgG type of immune response. Chronic inflammation and antigens on glandular epithelial cells lead to a progressive destruction with loss of the epithelial barrier function. Within the gastric mucosa, patches of intestinal metaplasia develop, which may be a risk factor for subsequent development of gastric carcinoma. Hyperacidity in duodenal ulcer patients induces gastric metaplasia in the duodenal bulb, which represents a target for H. pylori colonization and ulcer formation. H. pylori can be detected in the majority of patients with peptic ulcers and, compared to age-matched healthy people, it is also found more often in patients with dyspepsia and gastric carcinoma. Although H. pylori can be detected in healthy people, the marked reduction of the ulcer recurrence rate by eradication of H. pylori (80 percent versus 20 percent relapse within one year) suggests that H. pylori is a major risk factor for duodenal ulcer formation. The potential role of H. pylori in non-ulcer dyspepsia and carcinogenesis is under investigation. Current regimens aimed at eradicating H. pylori use a combination of several drugs that are potentially toxic. Since the risk of complications may exceed the potential benefit in most patients, eradication treatment should be limited to clinical trials and to patients with aggressive ulcer disease. New drug regimens, e.g., the combination of proton pump inhibitors with one antibiotic, may provide less toxic alternatives. Beyond ulcer treatment, effective and well-tolerated eradication regimens may have a place in prophylaxis of gastric carcinoma.
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PMID:Pathophysiology and clinical relevance of Helicobacter pylori. 134 Oct 68

Effects of dietary bile acids and their sodium salts on the development of pepsinogen-altered pyloric glands (PAPG) were examined in male WKY/N Crj rats initially given a single dose of 160 mg/kg body weight of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by gastric intubation. From week 3 the animals were administered basal diet containing 0.5% supplements of cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA) or their sodium salts (Na-C, Na-DC and Na-CDC), or 5% ascorbic acid (ASA) or its salt (Na-AS) for 18 weeks. The concentration of DCA and Na-DC was reduced to 0.3% from week 12. At week 20, animals were killed and the numbers of immunohistochemically-demonstrated PAPG were determined. Values were significantly higher with Na-C and Na-CDC than with the corresponding parent acids, and in the Na-C case PAPG development was greater than with MNNG alone. In addition, Na-CDC itself induced the numbers of PAPG significantly. These results suggest that bile salts are possible intrinsic promoters of gastric carcinogenesis. They were without effect, however, on forestomach lesions.
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PMID:Effects of various bile acids and their sodium salts on development of pepsinogen-altered pyloric glands in rats. 136 59

Morphological and phenotypical patterns of proliferative epithelial lesions induced in the gastric stump mucosa by duodenal content reflux after Billroth II partial gastrectomy (BII) were evaluated in rats. Control animals were either sham-operated or submitted at different times after BII to Roux-en-Y (RY) surgical procedure which prevents duodenal reflux. The lesions were analysed using routine haematoxylin and eosin staining, immunohistochemical staining for pepsinogen isoenzyme 1 and histochemical procedures for mucins (paradoxical Concanavalin A, galactose oxidase Schiff and sialidase galactose oxidase Schiff reactions). Mucosal hyperplasia (H) was observed in the group submitted to BII procedure 6 weeks after surgery. Adenomatous hyperplasia (AH) also appeared 6 weeks after induction of the reflux and its incidence and size increased until the 54th week of the experiment. RY procedure performed in the normal animals at the beginning of the experiment or at the 24th week after BII gastrectomy led to a significantly lower incidence of AH which was related to the moment of surgery. Most of H was due to pyloric mucosal hyperplasia. AH consisted mainly of gastric type glands but in some animals glands of the intestinal type were present probably originating from the intestinal mucosa. Six mucinous adenocarcinomas were observed, all of them of intestinal type. This study demonstrates that AH induced by BII procedure is a reversible lesion and that the anomalous epithelial proliferation in the stoma may lead to adenocarcinomas.
Carcinogenesis 1991 Aug
PMID:Reversibility of adenomatous hyperplasia in the gastric stump after diversion of bile reflux in rats. 186 Jan 64

The combined effects of low doses of various carcinogens and carcinogenesis modifiers on tumor development were investigated by using a wide-spectrum organ carcinogenesis model in F344 rats. These agents were administered as three groups: (1) a group of known hepatocarcinogens; (2) a group of nitroso compounds having various target organ specificities; and (3) a group of antioxidants having various inhibiting or enhancing activities depending on the target organ. Doses were used which were generally below the known effective level for the individual chemical. These groups of chemicals were administered with or without prior administration of N-diethylnitrosamine (100 mg/kg body wt., i.p.), N-methylnitrosourea (4 x 20 mg/kg body wt., i.p.) and dihydroxy-di-N-propylnitrosamine (0.1% in drinking water for 2 weeks). The hepatocarcinogen group in combination with various nitroso compounds increased the incidences of liver hyperplastic nodules and hepatocellular carcinomas. In contrast, incidences were clearly reduced when the hepatocarcinogens and/or the nitroso compounds were administered in combination with the antioxidants. For the urinary bladder, the combination with nitroso compounds and antioxidants enhanced cancer development, and the addition of hepatocarcinogens further increased tumorigenesis. For the glandular stomach, additive effects on the numbers of pepsinogen isozyme 1-altered pyloric glands, a putative preneoplastic lesion, were produced by the combination treatment of antioxidants and the nitroso compounds. No synergistic effects on tumor development were seen in other organs. The results of the present study demonstrated that combinations of various compounds at low doses can additively or synergistically exert either enhancing or inhibitory effects on the development of preneoplastic and neoplastic lesions in different organs in a single model having a wide spectrum of organ effects.
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PMID:Organ-specific modification of tumor development by low-dose combinations of agents in a rat wide-spectrum carcinogenesis model. 190 45

To assess the possibility of establishing an in vivo, medium-term bioassay system for gastric carcinogens and promoters, a total of 220 male WKY rats were divided into two groups. Group 1 animals were treated first with a single dose of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (160 mg/kg body wt) and starting 2 weeks later administrated one of five gastric carcinogens, a gastric promoter, one of five non-gastric carcinogens or no treatment, as a control, for 14 weeks. Saturated sodium chloride solution (1 ml) treatments were given by gastric intubation at weeks 4, 6, 8 and 10. Group 2 rats received 1 ml of DMSO instead of MNNG and were then treated in the same way as group 1. Analysis of pyloric mucosa sections for pepsinogen altered pyloric glands (PAPG) detected immunohistochemically after the animals were killed at week 16 revealed increased lesion numbers in group 1, with all gastric carcinogens and promoters examined. However, none of the five non-gastric carcinogens exerted any significant modification of PAPG development. The results strongly suggest that the experimental protocol consisting of the following four components: (i) adoption of PAPG as the end-point marker lesion; (ii) single dose of MNNG as initiator; (iii) test chemical administration for 14 weeks; and (iv) administration of saturated sodium chloride solution during the test chemical exposure, could be used effectively for the detection of gastric carcinogens as well as promoters of gastric carcinogenesis in a relatively short time period.
Carcinogenesis 1990 Nov
PMID:Enhancing effects of various gastric carcinogens on development of pepsinogen-altered pyloric glands in rats. 222 29

The effects of 8 weeks of oral administration of five different phenolic antioxidants, e.g. catechol (CC), resorcinol, hydroquinone (HQ), 2-tert-butyl-4-methylphenol (TBMP) and propylparabene (PP), on forestomach and glandular stomach epithelium of male F344 rats were evaluated using a combined immunohistochemical and histopathological approach. Treatment with CC and TBMP induced a significant elevation of DNA synthesis in the forestomach epithelium, associated with hyperplasia. CC administration also brought about an increase of DNA synthesis in the pyloric gland mucosa, cell proliferation in this case being reflected by an increment in the crypt height. In addition to causing an increase in the pepsinogen-isozyme-1-altered pyloric glands (PAPG), which are considered to be putative preneoplastic precursor lesions in the rat glandular stomach, CC treatment was associated with submucosal growth of pyloric mucosal cells tending to decreased pepsinogen isoenzyme 1 binding. However, DNA synthesis values in these latter areas were lower than in pyloric glands of the control group. In contrast, other phenolic compounds, resorcinol, HQ and PP, did not induce any changes in the stomach mucosa. The present results demonstrated strong proliferative responses in the stomach epithelium for CC and TBMP, indicative of promoting potential in both cases, and suggest that CC and TBMP may exert detrimental effects leading to promotion of stomach carcinogenesis or cancer development via an early proliferative response.
Carcinogenesis 1990 Mar
PMID:Early proliferative responses of forestomach and glandular stomach of rats treated with five different phenolic antioxidants. 231 Nov 86

An investigation of antioxidant-induced lesions in stomach epithelia was performed using F344 rats of both sexes. Histopathological changes, levels of DNA synthesis and pepsinogen isozyme 1 altered pyloric gland (PAPG) induction were assessed following 4 weeks oral administration of catechol (CC) or analogs such as hydroxyhydroquinone (HHQ), protocatechuic acid (PCA), protocatechualdehyde (PCAH), dopamine and DL-dopa. While epithelial hyperplasia of the forestomach was only observed in the groups given CC, DNA synthesis in this epithelium was increased in groups of both sexes treated with CC, HHQ or dopamine. In the glandular stomach, CC induced submucosal growth of pyloric mucosal cells and an increase in crypt height associated with an elevation of DNA synthesis and numbers of PAPG. In contrast, dopamine brought about significant reduction in DNA synthesis in the pyloric mucosa of both sexes. The other CC analogs did not exert any obvious influence on glandular stomach mucosa. Since cell proliferation is well correlated to tumor promotion, the results suggested that HHQ and dopamine may have promoting potential for rat two-stage forestomach carcinogenesis in common with CC, while dopamine might be expected to inhibit glandular stomach carcinogenesis.
Carcinogenesis 1990 Jun
PMID:Epithelial cell proliferation in rat forestomach and glandular stomach mucosa induced by catechol and analogous dihydroxybenzenes. 234 74


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