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

Sequential changes of numbers of pepsinogen 1 (Pg 1)-decreased pyloric glands (PDPG) detected by immunohistochemistry and of the incidence of gastric carcinomas were examined in five different strains of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG;CAS:70-25-7). Male SD (Crj:CD), WKY (WKY/NCrj), Lewis (LEW/Crj), Wistar (Crj:Wistar) and F344 (F344/DuCrj) rats (40 per strain), were given drinking water containing 100 micrograms/ml MNNG for 30 weeks and then normal tap water, and were killed at week 10, 30 and 50 of the experiment. Adenocarcinomas of the glandular stomach were found in nine of 15 SD rats (60%), in eight of 12 WKY rats (67%), in eight of 15 Lewis rats (53%), in three of 13 Wistar rats (23%) and in one of 18 F344 rats (6%) at week 50. These incidences of carcinomas in SD, WKY and Lewis were significantly higher (P less than 0.01) than that in F344 rats. From week 10, the numbers of PDPG in SD, WKY and Lewis rats were significantly greater (P less than 0.01) than that in F344 rats. From week 30, the numbers of PDPG in Wistar rats were also significantly greater (P less than 0.05-0.01) than that of F344. The susceptibility of rats to induction of gastric carcinoma by MNNG correlated with the susceptibility to induction of PDPG by MNNG in each strain, suggesting that induction of PDPG is a preneoplastic change in chemical gastric carcinogenesis.
Carcinogenesis 1988 Mar
PMID:Coefficient induction of pepsinogen 1-decreased pyloric glands and gastric cancers in five different strains of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine. 334 88

The effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the proliferative characteristics of the pyloric epithelium was investigated in ACI and Buffalo rats and their F1 rats, which are susceptible, resistant, and resistant, respectively, to gastric carcinogenesis by this chemical. After injection of bromodeoxyuridine (BrdUrd), DNA synthesizing cells in the pyloric epithelium were stained immunohistochemically with anti-BrdUrd antibody. The average number and range of distribution of cells labeled with BrdUrd in the pyloric glands were significantly larger in ACI rats than in Buffalo or F1 rats after administration of MNNG (83 micrograms/ml in the drinking water) for 2 or 16 weeks. In control rats given tap water for 2 weeks, there was no significant difference in these values in the three groups (Experiment 1). The distribution of cells that were labeled with [methyl-3H]MNNG in the pyloric epithelium was measured by histoautoradiography, and the distribution of cells double labeled with both [methyl-3H]MNNG and BrdUrd was also analyzed. Rats were given 83 micrograms/ml of MNNG in their drinking water for 2 weeks and then received [methyl-3H]MNNG by gavage and an injection of BrdUrd 2 and 1 h, respectively, before sacrifice. The average number of double labeled cells (i.e., replicating cells exposed to MNNG) was significantly larger in ACI rats than in Buffalo or F1 rats. In control rats given tap water without MNNG for 2 weeks, there was no significant difference in these values in the three groups (Experiment 2). Cells double labeled with [methyl-3H]MNNG and BrdUrd are considered to be cells with the potential to establish mutations (cell population at risk of MNNG-induced carcinogenesis). Our results show that, after MNNG treatment, the size of this cell population is larger in susceptible ACI rats than in resistant Buffalo and F1 rats. Thus, differential responses of the gastric mucosa to MNNG may be a key factor in the difference of susceptibility to gastric carcinogenesis between ACI and Buffalo rats.
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PMID:Differential proliferative response of gastric mucosa during carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in susceptible ACI rats, resistant Buffalo rats, and their hybrid F1 cross. 340 51

Sequential histologic changes of the stomach during carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG; CAS: 70-25-7) were studied in susceptible ACI and resistant BUF strain rats. Rats were given MNNG at a concentration of 83 micrograms/ml in their drinking water for 32 weeks and then tap water and were sacrificed sequentially between weeks 1 and 57. In ACI rats, erosions, regenerative changes, focal and slightly atypical changes, and diffuse and severe atypical changes were observed sequentially in the pyloric region during the period of MNNG administration, where adenocarcinomas were observed after the cessation of MNNG treatment. In BUF rats, the main histologic changes induced by MNNG were erosions and hyperplasia of the glandular portion of pyloric glands at the margin of erosions. After the cessation of MNNG treatment, the hyperplasia of the pyloric glands subsided and was followed by atrophy of these glands. The results suggested that the responses of the gastric mucosa to MNNG in ACI and BUF rats were qualitatively different.
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PMID:Sequential histologic changes during gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in susceptible ACI and resistant BUF rats. 346 13

The appearance of pyloric gland-type cells with a low pepsinogen isozyme 1 (Pg 1) content in the stomach mucosa of F344/Du rats during stomach carcinogenesis was examined by a combination of paradoxical concanavalin A (Con A) staining and immunohistochemical staining for Pg 1. Male F344 rats were given drinking water containing 100 micrograms N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7]/ml for 30 weeks and then normal tap water and were killed in week 10, 20, 30, 40, 50, or 70. Untreated rats were killed in week 30 or 70. Serial sections of pyloric mucosa were stained by paradoxical Con A staining and Pg 1 immunostaining. After MNNG treatment, tissues showing changes were classified into normal-looking pyloric mucosa with a low Pg 1 content, mucosa showing atrophic or hyperplastic changes, adenomatous hyperplasia, and adenocarcinoma. From the results of paradoxical Con A staining and Pg 1 immunostaining, the cells in lesions were classified into gastric types (surface mucous cell type and pyloric gland cell type) and intestinal types (intestinal-absorptive cell type and goblet cell type). In this experiment, the cells in lesions were mainly of the gastric cell types. All pyloric glands of control rats in weeks 30 and 70 contained class III mucins and had a high Pg 1 content demonstrated immunohistochemically. After MNNG treatment, class III mucin-positive pyloric glands with a low Pg 1 content in normal-looking pyloric mucosa were found from week 10; subsequently, their number increased with time. Changed mucosa was found from week 20, and the area of cells of the pyloric gland cell type with little or no Pg 1 in changed mucosa was about 30% of the area of cells of the pyloric gland cell type. Adenomatous hyperplasias were found from week 30; adenocarcinomas were found from week 50. Almost all cells of the pyloric gland cell type (greater than 95%) in areas of adenomatous hyperplasia and adenocarcinomas had little or no Pg 1 content. The present results suggested that the appearance of pyloric glands with a low Pg 1 content in normal-looking mucosa might be an immunohistochemically detectable preneoplastic change preceding morphologically detectable preneoplastic changes in stomach carcinogenesis.
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PMID:Immunohistochemical demonstration of pyloric gland-type cells with low-pepsinogen isozyme 1 in preneoplastic and neoplastic tissues of rat stomachs treated with N-methyl-N'-nitro-N-nitrosoguanidine. 347 May 52

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor-promoting phorbol diester, were determined with regard to the induction of esophageal cancer in Wistar rats following a low-dose initial administration of the esophageal carcinogen N-amyl-N-methylnitrosamine [(AMN) CAS: 13256-07-0]. The induction of esophageal cancer was enhanced by TPA given in drinking water after AMN administration; i.e., the incidence of developing esophageal cancers and the multiplicity (number of esophageal cancers per rat) were significantly higher in groups given TPA solution orally after an oral administration of AMN than in those given the AMN solution alone. The enhancement of carcinogenesis with TPA was not affected by the interval between the administration of AMN and the administration of TPA. However, pretreatment with TPA before AMN administration did not enhance the induction of esophageal cancer. Neoplasms were not detected in groups given only TPA or tap water. Because this approach is similar to the phenomenon of two-stage carcinogenesis in the skin, it should provide a meaningful experimental model for studying two-stage carcinogenesis in the esophagus.
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PMID:Enhancement of esophageal carcinogenesis induced in rats by N-amyl-N-methylnitrosamine in the presence of 12-O-tetradecanoylphorbol-13-acetate. 347 38

The F1 rats subjected to the influence of N-nitrosomethylurea (NMU) in dose of 20 mg/kg on the 21 day gestation as a result of postnatal disturbances of the thyroid function induced by long administration of thyroxin (3 mg/100 g, daily), methylthiouracil (MTU; 0.1% solution in tap water) or thyroidectomy have shown a decreased incidence of the nervous system tumours, but not of the kidney tumours, i. e. sites typical of NMU transplacental carcinogenesis. At the same time the NMU transplacental effect increased thyroid carcinogenesis, induced by the MTU postnatal application, which manifested in the increased incidence of malignant tumours of this site. The carcinogenic effect was observed in F2 rats, while some of them developed tumours of the nervous system (14.9%) and kidney (8.5%) but with lower incidence than in F1 (35.4; 14.1%, respectively). The same modifying factors (thyroxin, thyroidectomy, MTU) employed under the same conditions produca similar effect on carcinogenesis in F2 animals.
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PMID:[Effect of disordered thyroid function on the realization of the transplacental carcinogenic action of N-nitrosomethylurea in 1st- and 2d-generation rats]. 378 May 5

The effect of gastrectomy and duodenal reflux on gastric carcinogenesis was studied because gastrectomized patients may be considered at "high risk" for the development of gastric stump cancer. Wistar rats received N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (83 mg/liter) ad libitum in the drinking water for either four, eight, or twelve weeks. A control group received tap water. After MNNG administration animals were antrectomized. Antrectomy was not performed in a control group. Bowel continuity was restored either with a Billroth II (BIL) or with a ROUX en Y (ROUX) procedure. Duodenogastric reflux is possible after the BIL but not after the ROUX procedure. Eight months after the beginning of the experiment the stomachs of the animals were studied. In both operated and unoperated animals, the number of cancers observed was significantly related to the duration of MNNG administration. Animals receiving MNNG plus the BIL procedure had a significantly higher number of anastomotic cancers than the ROUX animals, indicating that duodenogastric reflux played a promotional role in gastric carcinogenesis. Three BIL gastrectomized rats not receiving the carcinogen had an adenocarcinoma on the anastomotic line further emphasizing the risk attached to the duodeno-gastric reflux.
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PMID:Gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine: role of gastrectomy and duodenal reflux. 392 34

The possibility that ascorbic acid, as a nucleophile, may inhibit mutagenicity induced by electrophilic metabolites of N-nitroso compounds was examined. In vitro data are presented to show that ascorbic acid does not decrease the mutagenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in a modified Ames bacterial mutagenicity system if deionized water is used to prepare the incubation medium. However, ascorbic acid prevents the mutagenicity of MNNG in vitro if added to bacteria in a medium prepared with either sterile tap water or deionized water and Cu2+ ions and that this antimutagenic response is blocked by EDTA. Additional in vitro experiments suggest that when ascorbic acid and Cu2+ ions are mixed in aqueous solution, H2O2 and free radicals derived from H2O2 are formed and these compounds may deactivate N-nitroso compounds. In vivo data are presented to show that ascorbic acid supplementation to guinea pigs (2000 mg/kg body weight/day) has no effect on the mutagenicity of N-nitrosodimethylamine, MNNG, N-methylnitrosourea and streptozotocin using the intrahepatic host-mediated bacterial mutagenicity assay. Additional in vivo studies demonstrate that simultaneous oral administration of ascorbic acid prevents the mutagenicity that follows the intragastric nitrosation of aminopyrine by nitrite while dietary pre-treatment with ascorbic acid does not. These findings suggest that ascorbic acid can block the intragastric formation of mutagenic N-nitroso compounds but that ascorbic acid has no effect on mutagenicity of N-nitroso compounds once they are formed.
Carcinogenesis 1985 Nov
PMID:Studies on the antimutagenic activity of ascorbic acid in vitro and in vivo. 393 30

Anatomical and functional vascular changes during rat urinary bladder carcinogenesis were studied by scanning electron microscopy of vascular casts, transmission electron microscopy of bladder capillaries, and fractional distributions of 51Cr-erythrocytes, 125I-human serum albumin, and 86RbCl which were used to determine vascular volume, permeability, and perfusion. Histopathological changes and focal capillary changes in vascular casts were measured quantitatively by an image analyzer. Male Wistar rats received 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 8 weeks and were then maintained on tap water without BBN for an additional 32 weeks. Simple hyperplasia was first seen at Week 2. The percentage of the area of hyperplastic epithelium increased to about 95% by Week 8 and then decreased to 4 to 6% at Weeks 20 or 40. Papillary or nodular hyperplasia was first seen at Week 6. The percentage of the area of papillary or nodular hyperplasia increased with time to 31.0% at Week 40. Papillary transitional-cell carcinomas were found from Week 20, increasing with time, and their incidence was 100% after Week 35. Vascular cast diameters of normal-looking capillaries were larger during than after BBN treatment. Type 3 vascular proliferations were found beneath papillary or nodular hyperplasia and cancer. Capillaries beneath simple hyperplasia and type 3 capillaries beneath capillary or nodular hyperplasia and cancers were fenestrated and dilated. Changes in vascular volume were independent of changes in permeability and perfusion. Best-fit curve analyses showed the maximum vascular volume at 8 weeks and minimum at 25 weeks, and the permeability maxima at 4 and 25 weeks with minima at 15 and 32 weeks. While 86Rb values correlated 125I values (r = 0.58), they were unstable in intermediate time periods. Changes of vascular volume were coincident initially with increased areas of dilated capillaries beneath simple hyperplasia and later with areas of type 3 capillary proliferation beneath papillary or nodular hyperplasia and cancer. Changes of vascular permeability were related to inflammation indices throughout the study. Increases in permeability were coincident with fenestrated capillaries beneath simple hyperplasia in early stages, and subsequently with fenestrated type 3 capillaries beneath papillary or nodular hyperplasia and cancer. BBN appears to cause alterations in vascular volume via induction of capillary dilation and also possibly by enhancing the responsiveness of host endothelium to angiogenic stimulation from neoplastic or preneoplastic tissues.
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PMID:Possible mechanistic roles of anatomical and functional vascular changes in rat urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine. 669 39

Sequential observations were carried out on the induction of preneoplastic lesions in the liver and the kidney. Rats were initially given N-ethyl-N-hydroxyethylnitrosamine (EHEN) in their drinking water (0.1%) for 3 days (Group 1), 1 week (Group 2) or 2 weeks (Group 3) or tap water (Group 4). Rats in Groups 1-3 were subjected to partial hepatectomy and unilateral nephrectomy (right side) 2 weeks after the end of EHEN treatment. Rats from these groups were killed in week 10, 20, 30 and 40 of the experiment. In the liver, the effect of EHEN in the induction of gamma-glutamyltranspeptidase (gamma-GT) positive foci and hyperplastic nodules (HN) was clearly dependent on the length of treatment. The preneoplastic lesions increased with the lapse of observation time. Changes measured as number of gamma-GT positive foci were 10-40 times greater than those measured as HN, especially among the small size range. Values for changes in Group 1 given 0.1% EHEN for 3 days were very low, indicating that this dose is close to the threshold. Two rats with hepatocellular carcinoma in Group 3 given EHEN for 2 weeks survived until week 40. In the kidney, tubular epithelial proliferations composed of cells with slightly basophilic cytoplasm and slightly atypical nuclei were tentatively named atypical cell foci (ACF). EHEN induced ACF, renal cell adenomas and renal cell carcinomas. The increase in the induction of ACF was dependent on the length of observation period but not on the length of treatment. Even though control rats (not treated with EHEN) also had ACF, their quantitative values were far less than the groups given EHEN and killed at week 40, indicating that a large number of ACF were induced by EHEN. Therefore, EHEN is good for experimental induction of preneoplastic lesions in the liver and kidney of rats. The experimental schedule for Groups 1 and 2 could be used as a shortterm screening test for promoters and the schedule for Group 3 as an assay for inhibitors.
Carcinogenesis 1983
PMID:Sequential observations on the appearance of neoplastic lesions in the liver and kidney after treatment with N-ethyl-N-hydroxyethylnitrosamine followed by partial hepatectomy and unilateral nephrectomy. 685 Sep 82


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