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

The purpose of this study was to find whether gastric resection enhances the incidence of carcinoma in the remaining part of the stomach. 66 male Wistar rats were subjected to stomach resection according to the Billroth I or the Billroth II method. These rats, as well as control animals with intact stomachs, were fed the carcinogen N-Methyl-N'-nitro-N-nitrosoguanidine (NG). -- 25 of 66 animals developed carcinomas in the gastric remnant. Precancerous lesions were seen in 18 rats. The tumours were characterized histologically as adenocarcinomas. They were almost exclusively localized in the region of the gastroenteral anastomosis. The process of tumour formation in the resected stomach was completed within 17-31 weeks on continuous administration of NG in a concentration of 120 mg/l in the drinking water. In contrast to these findings, the development of cancer in the intact stomach required on average 41 weeks under the same conditions of NG administration. However, with regard to the incidence of malignant changes, no significant difference was observed between animals undergoing the Billroth I method and those undergoing the Billroth II method.--The results suggest that the resected stomach of the rat is more susceptible to induction of cancer than the intac one. Exposure of the resected stomach to an oral carcinogen induces carcinogenesis predominantly in the anastomotic region.
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PMID:Susceptibility of the resected stomach to experimental carcinogenesis. 13 24

Epidemiologic and laboratory studies suggest that dietary fk actors, particularly high intake of fat and animal protein, and high concentration of bile acids and neutral sterols of the large bowel lumen are strongly associated with large bowel carcinogenesis. Such concepts guided our studies on animal models. Rats fed diets high in fat and/or protein had a higher incidence of DMH-induced large bowel tumors than rats fed standard diets. The source of fat and protein, animal vs. vegetable, had no major influence. High fat intake was associated with an increased excretion of fecal bile acids, particularly secondary bile acids, and neutral sterols. The repeated intrarectal doses of lithocholic acid or deoxycholic acid enhanced the development of MNNG-induced large bowel tumors in rats. Colostomized rats treated with intrarectal dose of MNNG had no tumors in the excluded segment. It suggests that luminal contents play a significant role in the induction of large bowel cancer. The results show that higher levels of bile acids in the large bowel lumen, resulting from high fat intake, exert a promoting effect on the development of large bowel cancer.
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PMID:Effect of bile acids and dietary fat on large bowel carcinogenesis in animal models. 68 37

Numerous nerve fibers containing various neuropeptides are found in gastric mucosa. They play an important role not only in regulation of gastric secretion, motility and microcirculation but also in regeneration and differentiation of gastric mucosa. These nerve fibers are reduced in chronic atrophic gastritis which is considered a lesion closely related to carcinogenesis. We investigated the effect of gastric gastric mucosal denervation (vagotomy) on gastric carcinogenesis by using two experimental rat models in which chronic atrophic gastritis is induced by duodenogastric reflux. At first, following administration of MNNG, vagotomy with duodenogastric reflux enhanced gastric carcinogenesis compared to reflux only. At second, in the model of gastric remnant in which no carcinogenic agent was given, both B-I and B-II gastrectomy with vagotomy showed an increase of carcinoma and/or adenoma at the anastomotic site compared to those without vagotomy. Moreover, in vagotomized groups, there were an increase of labeling index of PCNA positive cells in gastric mucosa and a marked reduction of intramucosal neutral mucin in PAS-Alcian blue staining. These results indicate that the lack of gastric mucosal innervation not only induces the decrease of gastric mucosal cell function and cytoprotection but also enhances the increase of immature cell regeneration.
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PMID:[Effect of gastric mucosal denervation on gastric carcinogenesis]. 136 55

DNA repair synthesis as estimated by the unscheduled incorporation of tritiated thymidine (3H-TdR) is a useful, economical, and rapidly performed bioassay for detecting DNA-damaging agents. The purpose of this study was to establish the method of MNNG induction and measurement of UDS in human gastric mucosal cells for further study of gastric carcinogenesis and its prevention. Normal gastric mucosal cells isolated from surgical specimens were exposed to various concentrations of MNNG in the presence of 5mM hydroxyurea and 10uCi/ml 3H-TdR in 1% FBS DMEM-F12 medium for 4 hours at 37 degrees C. Immediately following exposure to MNNG the capacity of gastric mucosal cells to undergo DNA synthesis was assayed by autoradiography. The results of the present study indicated that the gastric epithelial cells are capable of repairing MNNG-induced DNA damage. The UDS positive cells were revealed by increased 3H-TdR incorporation into each nucleus, and the UDS level was MNNG dose-dependent.
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PMID:[Unscheduled DNA synthesis (UDS) induced by N-methyl-N'nitro-N-nitrosoguanidine (MNNG) in human gastric mucosal cells]. 187

Large bowel carcinoma was induced in rats by injecting MNNG intrarectally, and changes in the large bowel mucosa prostaglandin (PG) with time were determined. The PGE2 levels of the colonic mucosa in a control group were 20.9 +/- 9.7 (pg/mg total protein) at 5 weeks, 25.5 +/- 9.7 at 10 weeks, 26.5 +/- 18.1 at 20 weeks, and 34.8 +/- 12.7 at 40 weeks. The PGE2 levels in the MNNG-treated group were 44.7 +/- 6.2 at 5 weeks, 43.1 +/- 14.9 at 10 weeks, 70.1 +/- 23.4 at 20 weeks, and 79.7 +/- 54.1 at 40 weeks. The intrinsic PGE2 levels of the noncancerous mucosa were thus significantly higher for the MNNG group than for the control group at all weeks. At 40 weeks, the PGE2 levels of cancer lesions were significantly high compared with those of the noncancerous area. In the cancerous lesions, 6-keto-PGF1 alpha and PGF2 alpha decreased and TXB2 increased significantly at 40 weeks. The observations demonstrated that PGE2 was implicated as a promoter in the development and proliferation of carcinoma in MNNG-induced large bowel carcinogenesis in rats.
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PMID:Investigation of colonic prostaglandins in carcinogenesis in the rat colon. 205 43

The effects of As2O3, MNNG and B(a)P on epithelia of human fetal tracheae and rat tracheae in organ culture were studied. In human fetal trachea, a small dose of arsenic (1 mumol As) induced hyperplasia of the epithelium; 3-9 mumol As induced hyperplasia and cellular atypia in the epithelium, and hyperplasia and squamous metaplasia in the adenoepithelium. Similar effects were not observed in rat tracheae. MNNG and B(a)P induced hyperplasia, squamous metaplasia and dysplasia in human fetal tracheal and rat tracheal epithelia respectively, and MNNG also induced hyperplasia and squamous metaplasia in human fetal tracheal adenoepithelium. The data suggest that 1) arsenic may be carcinogenic to the human respiratory tract but not to the rat; and 2) human tissues in organ culture are very useful for detecting carcinogens and for studying carcinogenesis.
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PMID:[Effects of As2O3, MNNG and B(a)P on epithelia of human fetal tracheae and rat tracheae in organ culture]. 215 96

In prostaglandin E2 (PGE2)-, pirenzepine-, and indomethacin-administered rats, the incorporation of N-[methyl-3H]-N'-nitro-N-nitrosoguanidine ([methyl-3H]MNNG) into gastric mucosal DNA was measured quantitatively by liquid scintillation counting after intragastric instillation of [methyl-3H]MNNG. The amount of incorporation was 25.4 +/- 5.9 pmol/mg DNA in control rats, 11.7 +/- 3.8 pmol/mg DNA in PGE2-administered rats, 6.2 +/- 5.6 pmol/mg DNA in pirenzepine-administered rats, and 42.9 +/- 14.4 pmol/mg DNA in indomethacin-administered rats. PGE2 and pirenzepine significantly decreased the incorporation as compared with the control group. In contrast, indomethacin increased the incorporation. In addition, gastric mucosa of these drug-treated rats was studied histochemically. PGE2 and pirenzepine increased secretion of gastric mucus whereas indomethacin decreased it. It is possible that gastric mucus has a protective effect not only against ulcerogenic agents but also against carcinogens. It is considered that gastric mucus plays an important role in the defense mechanism against carcinogenesis.
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PMID:Effect of gastric mucus on the uptake of the carcinogen MNNG by gastric mucosal DNA. 221 37

The effect of an exogenous synthetic prostaglandin analogue, 16,16-dimethyl prostaglandin E2 (16,16-dm-PGE2), as well as the effect of endogenous prostaglandin synthesis inhibition by a cyclooxygenase inhibitor, flurbiprofen, on chemically induced gastric carcinogenesis has been investigated in rats. Carcinogenesis was induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; CAS:70-25-7). Animals were divided into six groups: Group I, treatment with MNNG alone; Group II, treatment with 16,16-dm-PGE2 plus MNNG; Group III, treatment with flurbiprofen plus MNNG; Group IV, treatment with 16,16-dm-PGE2 alone; Group V, treatment with flurbiprofen alone; and Group VI, controls. Treatment with high doses of MNNG resulted in rapid development of malignant tumors originating from the glandular epithelium of the stomach and duodenum in animals of all groups receiving the carcinogen. The first gastric adenocarcinoma infiltrating the muscularis proper was detected after 139 days in an animal treated with a combination of MNNG and flurbiprofen. The incidence of infiltrating adenocarcinoma and the incidence of all neoplastic lesions of the glandular stomach were both significantly higher in animals treated with a combination of MNNG and flurbiprofen compared with treatment by MNNG alone or in combination with 16,16-dm-PGE2 (P less than 0.05 and P less than 0.001). The difference in tumor incidence between the last two groups was not significant. The first duodenal adenocarcinoma was detected on Day 114 in another animal of the group treated with MNNG plus flurbiprofen. When compared with the group treated with MNNG plus 16,16-dm-PGE2, significantly more animals developed duodenal adenocarcinoma when treated with MNNG plus flurbiprofen (P less than 0.005) or with MNNG alone (P less than 0.05). Results of this study indicate that inhibition of endogenous prostaglandin synthesis favors development of adenocarcinoma in the glandular stomach of rats. Vice versa, the addition of an exogenous prostaglandin analogue inhibits the development of duodenal adenocarcinoma. This protective effect of prostaglandins may be due to an increase of the thickness of the mucus gel covering the glandular epithelium, thereby preventing access of carcinogen to the mucosa.
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PMID:Effect of flurbiprofen and 16,16-dimethyl prostaglandin E2 on gastrointestinal tumorigenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats: glandular epithelium of stomach and duodenum. 229 78

Two new mouse epidermal cell lines have been isolated and characterized as target cells for three chemical carcinogens. The ability to grow these cells at low density (approximately 5 clonogenic cells/cm2) has permitted more precise quantitation of chemical carcinogen-induced changes in epidermal differentiation. The cell lines, designated 291 and 271c, retain the property previously observed in primary cultures of mouse epidermal cells, that is the regulation of terminal differentiation by extracellular Ca2+ ion. Altered response to extracellular Ca2+ after carcinogen treatment of these cells is the basis of the assay endpoint. Other normal properties demonstrated by these cells are keratin immunofluorescence patterns, ability to form cornified envelopes in response to Ca2+ and a lack of tumorigenicity. Both of the lines have high cloning efficiencies (up to 20%) and characteristic epidermal morphology. Their chromosome number, however, is near tetraploid. Dose response studies indicated an increase in colonies with altered response to Ca2+ proportional to the dose of three chemical carcinogens: DMBA 0.001-0.5 microgram/ml X 24 h, MCA 0.01-5 micrograms/ml X 24 h and MNNG 0.01-0.2 micrograms/ml X 1 h. The optimized assay protocol has provided a reproducible means of quantitating carcinogen-altered epidermal cells relative to carcinogen dose, and of isolating cell clones for studies of altered differentiation in carcinogenesis and chemotherapy.
Carcinogenesis 1985 Sep
PMID:Mouse cell clones for improved quantitation of carcinogen-induced altered differentiation. 241 40

Pepsinogen mRNA is shown to be the major fraction of rat poly (A)+RNA. It codes polypeptide with molecular weight of about 45 kD. Changes in the pepsinogen mRNA content at the early stage of carcinogenesis are nonspecific and are due to the toxic effect of MNNG. Steady shifts in the quantity of pepsinogen mRNA are found between the 1st and 3d months. Pepsinogen mRNA content decreases down to the half of the normal one between the 3d and 6th months. A quantity of RNA capable to be a template for pepsinogen synthesis is reduced by more than 90% in the MNNG induced tumour. The pepsinogen production defect in gastric mucosa neoplasia is mainly due to pepsinogen mRNA synthesis damage.
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PMID:[Changes in the content of pepsinogen messenger RNA in the gastric mucosa of rats during N-methyl-N'-nitro-N-nitrosoguanidine-induced carcinogenesis]. 243 20


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