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

The intriguing observation has been made that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] receptors are present in tissues not involved in calcium homeostasis and that 1,25(OH)2D3 exerts an antiproliferative, differentiation-promoting action in a variety of cancer cell lines, including cells of the large intestine. It was therefore deemed of interest to study 1,25(OH)2D3 expression and biological activity in a murine model of colon carcinogenesis. Colon carcinogenesis was induced in male rats by the sequential administration of 1,2-dimethylhydrazine dihydrochloride (DMH). Levels and binding characteristics of 1,25(OH)2D3 receptors were assessed in control and DMH-treated rat colonic mucosal high-speed supernatants. In concurrent studies, 1,25(OH)2D3 was administered (s.c., 400 ng/rat) prior to, together with and after DMH challenge and the activity of ornithine decarboxylase (ODC), a growth-related DMH-induced enzyme, was determined in colonic cytosols. Serum Ca2+ levels were measured concurrently. Rats submitted to identical treatment schedules were killed 10 weeks after termination of DMH administration and the whole colon was opened and examined for tumors. The results show that (i) rat colonic mucosa possesses a single class of high-affinity 1,25(OH)2D3 receptors; (ii) DMH administration provokes a marked reduction (50%) in 1,25(OH)2D3 binding sites without affecting Kd values; (iii) DMH administered concurrently with 1,25(OH)2D3 suppressed the vitamin D-induced hypercalcemia and restored serum Ca2+ concentrations to basal levels; and (iv) 1,25(OH)2D3 delivered prior to DMH challenge obliterated the typical DMH-induced early colonic ODC activity peak and markedly reduced (50%) the number of colon adenocarcinomas. The present findings indicate that a colon-specific potent carcinogen interferes with the biological expression of 1,25(OH)2D3 and that vitamin D administered prior to a carcinogenic insult is able to reduce significantly the incidence of colon tumors, presumably acting as an antiproliferative or differentiation-promoting agent.
Carcinogenesis 1992 Dec
PMID:A protective role of 1,25-dihydroxyvitamin D3 in chemically induced rat colon carcinogenesis. 133 76

The chemopreventive effect of 40% and 80% maximum tolerated dose (MTD) levels of 1,4-phenylenebis(methylene)selenocyanate (p-XSC) administered in the diet during the initiation phase (2 weeks before, during, and up to 3 days after carcinogen administration) and the post-initiation phase (3 days after carcinogen treatment until termination) of azoxymethane (AOM)-induced colon carcinogenesis was studied in male F344 rats. The MTD of p-XSC was determined in male F344 rats and found to be 50 ppm. Beginning at 5 weeks of age, all animals were divided into various experimental groups (42 rats/group) and fed the high-fat semipurified diet or diets containing 20 (40% MTD) and 40 (80% MTD) ppm p-XSC. At 7 weeks of age, all animals (30 rats/group) except the vehicle-treated groups (12 rats/group) were administered s.c. injections of AOM (15 mg/kg body weight/week for 2 weeks). Three days after the second injection of AOM or vehicle (normal saline), groups of animals fed the p-XSC diets and control diet were transferred, respectively, to control diet and p-XSC diets and continued on these diets until the termination of the study. All animals were necropsied during the 36th week after AOM treatment. Colonic mucosal prostaglandin E2 and selenium-dependent glutathione peroxidase were measured in animals fed the control and p-XSC diets at the termination of the study. The results indicate that 40 ppm p-XSC administered during the initiation phase significantly inhibited the colon tumor incidence (percentage of animals with tumors). Dietary p-XSC administered at 20 and 40 ppm levels during the initiation phase significantly inhibited colon tumor multiplicity (tumors/animal and tumors/tumor-bearing animal). Colon tumor incidence and multiplicity were significantly reduced in groups fed 20 and 40 ppm p-XSC diets at the postinitiation phase of carcinogenesis. Colonic mucosal selenium-dependent glutathione peroxidase activity was increased, and prostaglandin E2 was reduced in animals fed the p-XSC diet compared to animals fed the control diet. Whereas the precise mechanisms of p-XSC-induced inhibition of colon carcinogenesis remain to be elucidated, it is likely that the effect during the initiation and postinitiation phases may be due to alteration in carcinogen metabolism and to modulation of prostaglandin synthesis and selenium-dependent glutathione peroxidase activity.
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PMID:Chemoprevention of colon carcinogenesis by the synthetic organoselenium compound 1,4-phenylenebis(methylene)selenocyanate. 139 88

This study explores the role of sutures and the healing colonic wound in experimental carcinogenesis. One hundred sixty rats underwent surgery with colotomy and repair using silk, steel, or Vicryl (Ethicon, Somerville, NJ) sutures or a sutureless technique. Forty rats had a sham procedure. All animals received azoxymethane for 12 weeks at a dose of 10 mg/kg/week. Half the rats commenced carcinogen before surgery, and half commenced it eight weeks after surgery. Animals with anastomotic tumors were found in 46 percent of the sham group (P less than 0.05 cf. sutured), 41 percent of the sutureless group (P less than 0.02 cf. sutured), and 68 percent of the sutured group. The corresponding figures for anastomotic carcinoma were 9 percent (P less than 0.001 cf. sutured), 22 percent, and 38 percent. No significant differences in tumor yield were noted among the different sutures. However, several differences were noted between the two carcinogen models. In those animals that received surgery first, there was a higher incidence of anastomotic tumors (P less than 0.002) and cancers (P less than 0.0001) in the sutured and sutureless groups, and those tumors that occurred in the sutured group were considerably larger than in those that had carcinogen first (15.9 mm cf. 4.9 mm; P less than 0.0001). Overall, all sutures seem to enhance anastomotic tumor formation, and we would suggest that a sutureless anastomosis may diminish this risk.
Dis Colon Rectum 1992 Sep
PMID:Experimental carcinogenesis at sutured and sutureless colonic anastomoses. 151 53

Local tumor recurrence following restorative surgery for colorectal cancer may occasionally result from the promotion of a neoplastic lesion in a zone of proliferative instability adjacent to the anastomosis. The aim of this study was to compare the influence of three anastomotic suture materials, including stainless steel (as a model of surgical stapling), on colorectal carcinogenesis in an experimental animal model. The transmural implantation of stainless steel sutures into the distal descending colon of albino Swiss rats during the postinitiation phase of tumor induction resulted in significantly fewer animals exhibiting perianastomotic tumors 12 weeks later (3 of 21 animals) when compared with either polyamide (Nurolon; Ethicon, Edinburgh, United Kingdom) (14 of 20 animals; P less than 0.001) or polyglycolic acid (Dexon Plus; Davis and Geck, Gosport, United Kingdom) sutures (17 of 21 animals; P less than 0.001). The findings were similar when the same materials were used to resuture a longitudinal colotomy. For both operative procedures, the type of suture material had no influence on the incidence of large bowel tumors distant from the anastomotic site. These results suggest that stainless steel staples may promote fewer perianastomotic large bowel tumors than certain more conventional suture materials and, therefore, may be safely employed in colorectal cancer surgery.
Dis Colon Rectum 1991 Nov
PMID:Anastomotic suture materials and experimental colorectal carcinogenesis. 165 55

Jejunoileal bypass (JIB) has been a widespread operation for treatment of morbid obesity. Bile acids are regarded as cofactors in the carcinogenesis of the colon, and, since intestinal bypass involves increased exposure of bile acids to the large intestinal mucosa, JIB has been postulated to increase the risk for colorectal carcinoma. In experimental studies on animals, the results have indicated an increased frequency of induced carcinomas, but in clinical series only one patient with colon carcinoma has been reported. Thirty women, operated on with JIB 11 to 17 years earlier, were examined by colonoscopy with multiple biopsies, systematically taken for histologic evaluation and flow cytometric DNA analysis. In only one patient, low-grade dysplasia was detected in an initial adenomatous lesion but was not visible macroscopically. No DNA aneuploidy was found. In a control group of 11 patients examined for non-neoplastic disease, neither dysplasia nor aneuploidy was diagnosed. Within 17 years postoperatively, we have, by these methods, not been able to verify any colorectal malignant transformation in patients operated on with JIB. However, since carcinogenesis is a long process, further surveillance will be demanded before an increased risk for colorectal carcinoma can be excluded.
Dis Colon Rectum 1992 Mar
PMID:Colorectal cancer risk after jejunoileal bypass: dysplasia and DNA content in longtime follow-up of patients operated on for morbid obesity. 174 70

Carcinogen-induced aberrant crypts (AC) of the colon are a precancerous state that leads to malignancy. The inhibition of AC formation by chemopreventive agents was evaluated in this study. Colon AC were induced by 1,2-dimethylhydrazine (DMH) in 3 weeks in CF1 mice. The cecum of the large intestine of CF1 mice did not produce more than one AC focus per animal. The effect of DMH and that of the inhibitors in this part of the large bowel were essentially similar to the vehicle control and inhibitor-only controls. The response of DMH treatment in the colorectal portion of the large bowel was found to be different from that of the cecum. The DMH treated mice had 13-17 foci per animal in three different experiments. The average number of AC per focus was greater than one in all three experiments performed. None of the inhibitor-only control animals nor the cottonseed oil vehicle control animals developed AC focus in the colorectal or the cecal part of the large bowel. The known inhibitor of colon carcinogenesis 3-butyl-4-hydroxyanisole reduced DMH-induced average AC formation by 10 and 46% at 1 and 4 mg per dose, respectively. The inhibitors 2-n-butylthiophene and phenylpropylisothiocyanate reduced DMH-induced average AC formation greater than 34 and greater than 40% respectively. The postulated inhibitor 2-n-octylthiophene, which is an eight-carbon homolog of 2-n-butylthiophene, similarly reduced DMH-induced AC formation. The known colon carcinogenesis inhibitor dehydroepiandrosterone, in contrast, has no effect. The inactivity of dehydroepiandrosterone to inhibit colon AC formation was attributed to its mechanism of inhibitory action, which differs from that of the phenol, isothiocyanate and thiophenes. The short duration that is required to produce quantifiable results suggests that the reduction of carcinogen-induced AC formation may be developed into a useful prescreening assay for potential chemopreventive agents against colon cancer.
Carcinogenesis 1991 Dec
PMID:Reduction of aberrant crypt formation in the colon of CF1 mice by potential chemopreventive agents. 174 33

The effect of dietary menhaden oil containing omega-3 fatty acids and corn oil rich in omega-6 fatty acids fed during the initiation and/or postinitiation stages of colon carcinogenesis was investigated in male F344 rats. At 5 weeks of age, all animals were divided into seven groups (39 rats/group) and fed the semipurified diets containing 5% corn oil (LCO), 23.5% corn oil (HCO), or 18.5% menhaden oil plus 5% corn oil (HFO). At 7 weeks of age, all animals except the vehicle (normal saline)-treated groups were given two weekly s.c. injection of azoxymethane (AOM) at a dose rate of 15 mg/kg body weight, once weekly. Three days after the second injection of AOM, groups of animals fed LCO, LCO, HCO, HCO, HCO, HFO, or HFO diets were transferred, respectively, to LCO, HCO, LCO, HCO, HFO, HCO, or HFO and continued on these diets until termination of the experiment. All animals were necropsied 42 weeks after carcinogen treatment. Body weights of animals fed various experimental diets during the initiation and postinitiation periods were comparable. As expected, the HCO diet fed during the postinitiation period significantly increased the AOM-induced incidence and multiplicity of colon adenocarcinomas, whereas the HCO diet fed during the initiation phase of carcinogenesis had no effect. Colon tumor incidence and multiplicity were significantly reduced in groups fed the HFO diet at either initiation and/or postinitiation phases of carcinogenesis as compared with those fed the HCO diet. Whereas the precise mechanisms producing the difference between the high menhaden oil (HFO) diet as compared with high corn oil (HCO) diet remain to be elucidated, it is likely that the effect during the initiation and postinitiation phases may be due to alteration in carcinogen metabolism and to modulation of prostaglandin synthesis, respectively.
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PMID:Effect of diets high in omega-3 and omega-6 fatty acids on initiation and postinitiation stages of colon carcinogenesis. 182 Oct 94

67 segments of rectum and sigmoid removed surgically because of carcinoma were examined: the surface of intestinal mucosa stained with methylene-blue was studied in order to determine the number and localization of focal changes in the macroscopically unchanged areas. Colon microscopy was performed clinically in 24 patients with carcinoma of the rectum and in 24 control individuals. 28 hyperplastic polyps and 1037 microscopic hyperplastic foci were found in operative material. An active metabolism is established by means of electron autoradiography in the cells of hyperplastic focus. Areas of dysplastic epithelium were rarely found in big hyperplastic polyps. Areas of diffuse hyperplasia (transitional mucosa) with crypt deepening and presence of a high number of goblet cells were found near tumour. A certain role of hyperplastic processes in carcinogenesis is forwarded. Numerous microscopic changes in the mucosa epithelium may testify against the carcinoma development de novo.
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PMID:[Hyperplastic changes in the mucosa in colon cancer]. 187 90

Overexpression of the glutathione S-transferases (GSTs) and their involvement in the detoxification of anticancer agents has prompted numerous investigations of the enzyme activity of human tumor tissue. This study represents an in-depth evaluation of the contribution of patient history and pathological status to the GST activity of various human tissues. GST activity was elevated significantly in tumors of the lung, breast and colon as compared to unmatched and matched normal tissue from the same organ. The GST activity of primary breast tumors varied significantly with the stage of the tumor. Breast tumors previously treated with both radiation and chemotherapy had significantly lower levels of GST activity than untreated tumors. Neither progesterone nor estrogen receptor content was associated with the GST activity in primary breast tumors. Colon metastases possessed higher levels of GST activity than primary colon tumors but enzyme activity was independent of the Duke's classification of the tumor. Only tumors of the left colon had levels of GST activity that were higher than those of adjacent normal mucosa. No relationship was evident between either age or sex and the GST activity of any of the tissues examined. GST activity levels may reflect the site-specific ability of tissues to provide cellular protection against xenobiotics.
Carcinogenesis 1991 Oct
PMID:Contribution of patient history to the glutathione S-transferase activity of human lung, breast and colon tissue. 193 78

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.
Dis Colon Rectum 1991 Jul
PMID:Investigation of colonic prostaglandins in carcinogenesis in the rat colon. 205 43


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