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

The effect of four dose levels of piroxicam administered during different stages of colon tumor development was studied in male F344 rats to obtain a data base on the efficacy of piroxicam as an inhibitor of colon carcinogenesis. Piroxicam was added at levels of 25, 50, 75, and 150 ppm to the NIH-07 open-formula diet and fed to male F344 rats starting 1, 13, and 23 wk after the carcinogen administration. At 7 wk of age, while the animals were consuming the control diet, all animals except the vehicle-treated controls were given s.c. injection of azoxymethane (CAS:25843-45-2; 29.6 mg/kg body weight, once) to induce intestinal tumors. Forty wk after AOM injection, all animals were necropsied, and tumor incidences were compared among the various dietary groups. Colon tumor incidence (percentage of animals with tumors) was inhibited in a dose-dependent manner in rats fed the diets containing 25, 50, 75, and 150 ppm piroxicam starting 1 and 13 wk after carcinogen treatment. The colon tumor incidences in animals fed the diets containing 0, 25, 50, 75, and 150 ppm of piroxicam starting at 1 wk after carcinogen treatment were 89, 61, 58, 50, and 39%, respectively. When the diets containing 0, 25, 50, 75, and 150 ppm were fed 13 wk after carcinogen treatment, the colon tumor incidences were 89, 69, 69, 44, and 33%, respectively. Colon tumor multiplicity (tumors/animal; tumors/tumor-bearing animal) was also significantly inhibited in animals fed the diets containing 25 to 150 ppm piroxicam starting 1 and 13 wk after carcinogen administration. The number of colon tumors/animal was inhibited by about 80 to 84% in animals fed the 150 ppm piroxicam diet. When the diets containing different levels of piroxicam were fed 23 wk after carcinogen treatment, the colon tumor incidence was significantly inhibited in animals fed the 75 and 150 ppm piroxicam diets. The colon tumor incidences in animals fed the diets containing 0, 25, 50, 75, and 150 ppm were 89, 78, 67, 64, and 64%, respectively. The colon tumor multiplicity (colon tumors/animal) was slightly but significantly inhibited in animals fed the diets containing 25 to 150 ppm piroxicam. The results of this study demonstrate that increasing levels of piroxicam in the diet, when fed 1 or 13 wk after carcinogen insult, inhibit colon tumor incidence in a dose-dependent manner.
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PMID:Dose-related inhibition of colon carcinogenesis by dietary piroxicam, a nonsteroidal antiinflammatory drug, during different stages of rat colon tumor development. 365 39

Recent epidemiologic findings indicate that relative risk of colon cancer is augmented with increasing proportion of time spent on sedentary occupations, and reduced with occupations requiring high levels of work-related physical activity. Therefore, the influence of exercise on experimental colon carcinogenesis was investigated. Spontaneous running wheel activity was related to incidence of 1,2 dimethylhydrazine (DMH) colon tumor induction. Colon tumor incidence was significantly reduced in animals that were allowed spontaneous wheel activity throughout the period of DMH tumor induction vs standard housed controls (p less than 0.05), indicating that, in the rat, physical activity protects against colon tumorigenesis. Further comparisons reveal a mild positive association (p = 0.07) between activity and incidence of tumors in the left colon. These results are in accord with epidemiologic findings indicating reduced colon cancer risk with increased physical activity. Possible mechanisms for the protective influence of physical activity on tumorigenesis include reduction in fecal pH, body weight and increased antioxidant enzyme activity. To the extent that epidemiologic associations between colon cancer and activity are inclusive of the multidimensional nature of physical activity, animal models such as that utilized in this experiment can be utilized for investigating the etiologic potential, or strength of association in variables that have been epidemiologically associated with colon cancer risk.
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PMID:The influence of physical activity in 1,2 dimethylhydrazine induced colon carcinogenesis in the rat. 367 72

This investigation was based on an epidemiologic association of milk consumption and decreased intestinal cancer risk. Furthermore, there is also some indirect evidence that calcium supplementation in humans and animals may decrease colon cancer risk and that calcium, by inference, may be the protective factor in milk. In order to investigate these associations in a controlled laboratory setting, dietary supplementation of low fat dried milk (37 g/kg diet; N = 18) and calcium carbonate (40 mg/kg rat/day; N = 17) were compared separately to regular diet controls in the rat-dimethylhydrazine colon carcinogenesis model. The results of this investigation showed that neither milk-supplemented rats nor calcium carbonate-supplemented rats had fewer DMH-induced colorectal (P = .374) or total gastrointestinal tumors (P = .291) than did regular diet controls (N = 10; by analysis of variance [ANOVA]). Milk supplementation did result in a significant decrease in tumor burden when measured by incidence of metastases (P = .035) and of intestinal obstruction (P = .011; by chi-square test), when compared with calcium-supplemented and control rats. Though this implies that milk supplementation provides protection against some aspects of carcinogenesis of the colon, in rats fed low fat diets, this does not appear to be mediated through the calcium content of milk.
Dis Colon Rectum 1987 Dec
PMID:The effect of dietary milk and calcium on experimental colorectal carcinogenesis. 369 Dec 67

The effect of cholecystectomy on colon carcinogenesis induced by methylazoxymethanol (MAM) acetate was examined in four groups of Syrian golden hamsters. For the sexes combined, the incidences of total large intestinal neoplasms and adenomas in Group 1, which received cholecystectomy and a single intravenous injection of MAM acetate (20 mg/kg body weight), were significantly higher than those of hamsters in Group 2, which were given MAM acetate alone. The combined multiplicities of total large intestinal neoplasms from male and female hamsters, and the multiplicities of those in females of Group 1 were also significantly higher than those in animals in Group 2, respectively. No intestinal tumors were observed in hamsters in Group 3 (cholecystectomy alone) or Group 4 (untreated control). These results indicate an enhancing effect of cholecystectomy on MAM acetate-induced large intestinal carcinogenesis in hamsters.
Dis Colon Rectum 1986 Aug
PMID:Enhancing effect of cholecystectomy on colon carcinogenesis induced by methylazoxymethanol acetate in hamsters. 373 64

Protein kinase C (PKC) is a Ca2+- and phospholipid-dependent protein kinase which is implicated in tumor promotion, since it has been demonstrated to be a high affinity receptor for tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate. Colon carcinogenesis appears to proceed through distinct stages of initiation and promotion. The present studies show that PKC and calcium-dependent protein kinase specific activities are reduced in human colon carcinomas when compared to their normal adjacent colon mucosa. There were significantly higher Ca2+-dependent protein kinase and PKC specific activities observed in both the cytosolic and particulate fractions of the normal mucosa relative to the corresponding values obtained with the carcinoma fractions. The average specific activity ratios were 5.1 (normal cytosolic/carcinoma cytosolic) and 3.7 (normal particulate/carcinoma particulate) for PKC. PKC activity was reduced in the carcinoma tissues with respect to both protein and tissue weight. The percentage of Ca2+-dependent protein kinase and PKC activities that were present in the particulate fraction of each of the samples varied considerably among tissues, and in general there was no systematic difference between the carcinoma and normal mucosa samples. However, in the carcinoma samples that contained an extensive admixture of benign adenomatous tissue, the particulate fractions consistently contained greater than 60% of the total Ca2+-dependent protein kinase and PKC activities. The present studies indicate that colon carcinogenesis is associated with alterations in cellular levels of protein kinase activities.
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PMID:Altered levels of protein kinase C and Ca2+-dependent protein kinases in human colon carcinomas. 382 92

Colon epithelium is made up of two general classes of cells, surface cells which are post-mitotic and crypt cells which contain the proliferative population. Their relative vulnerability to environmental damage and ability to perform DNA repair are important issues in colon carcinogenesis. DNA damage and repair was studied by the nucleoid sedimentation method in freshly isolated crypt cells for comparison with previous studies of post-mitotic surface epithelial cells. Suspensions of crypt cells were isolated from preparations of mouse colon by a series of sequential incubations in buffer containing 1.5 mM EDTA. Treatment of crypt cells for 30 min with 1.2 X 10(-6) M methyl methane sulfonate (MMS), photoaffinity labeling with 1 X 10(-6) M ethidium monoazide, lithocholic acid (2.5 X 10(-4) M) treatment for 1 h or X-irradiation at 1500 rads resulted in single-strand breaks in the DNA, which were repaired after 2 h of additional incubation. Interestingly, X-rays at 1000 rads and lithocholic acid (LA) (2.5 X 10(-6) M) after 30 min incubation failed to produce the detectable shift in nucleoid sedimentation characteristic of single-strand breaks, perhaps due to rapid repair by these proliferative cells. UV-irradiation failed to provoke strand incision as was also observed for the superficial post-mitotic cells in the previous studies. These studies showed the feasibility of studying DNA damage and repair processes in these two classes of colon epithelial cells in response to specific carcinogenic insult.
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PMID:DNA damage and repair in epithelial (mucous) cells and crypt cells from isolated colon. 397 70

The relationship between cholecystectomy and large-bowel cancer development was investigated in animal models. Female ICR mice underwent cholecystectomy, and received 15 weekly intragastric administrations (Experiment 1) or 10 weekly subcutaneous injections (Experiment 2) of 15 mg/kg body weight of large-bowel carcinogen 1,2-dimethylhydrazine (DMH). Autopsy at 28 weeks after surgery showed that cholecystectomized mice had a nonsignificantly increased incidence of large-bowel carcinomas, compared to sham-operated and/or unoperated control mice (85 vs. 64 percent in Experiment 1; 31 vs. 16 and 20 percent in Experiment 2). Cholecystectomy alone without DMH treatment did not produce any cancer. Cholecystectomized mice excreted a significantly increased level of primary bile acids but an unchanged level of secondary bile acids in the feces, compared with unoperated control mice. It is obvious that cholecystectomy enhanced the development of DMH-induced, large-bowel carcinomas along with the change of fecal bile acid composition, suggesting that changes of bile acid metabolism after cholecystectomy may enhance or promote large-bowel carcinogenesis in man as well. This association of cholecystectomy and large-bowel cancer is not a strong one, however, as presented in epidemiologic as well as experimental studies.
Dis Colon Rectum 1985 Jan
PMID:The correlation between cholecystectomy and fecal bile acids, and large-bowel cancer induced with 1,2-dimethylhydrazine in mice. 397 96

There is an epidemiologic association between beer consumption and rectal cancer. Beer and ethanol were tested in the rat-dimethylhydrazine (DMH) experimental carcinogenesis model in order to verify this observation. Ethanol was found not to affect the number of colonic tumors induced by DMH (86 vs. 77 controls, P = 0.764). In rats fed beer and treated with DMH, there was a decrease in gastrointestinal tumor induction (P = 0.043). This instance then becomes one of many in which conclusions drawn from epidemiologic studies have been contradicted when subjected to analysis in an experimental colon carcinogenesis model.
Dis Colon Rectum 1985 Jun
PMID:Neither dietary ethanol nor beer augments experimental colon carcinogenesis in rats. 400 41

The modulatory effect of IPR on the initiation and promotion of DMH-induced colon carcinogenesis was investigated using CF-1 young adult female mice. IPR given soon after each of weekly DMH injections inhibited the initiation phase of colon carcinogenesis when the cumulative dose of DMH was small. However, such inhibition was not observed when the cumulative dose of DMH was doubled. Colon neoplasms that developed in spite of IPR treatments seemed to infiltrate the colon wall earlier as compared to those without IPR. On the other hand, IPR did not appear to affect the promotion phase of colon carcinogenesis.
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PMID:Modulation of symmetrical 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis by isoproterenol (IPR). 403 78

High incidences of breast and colon tumors are associated with high dietary fat intake. The importance of specific fat type and of other nutrients that interact with fat, as well as the mechanisms by which fat acts, is being investigated in animal models. The amount and type of dietary fat influence mammary gland carcinogenesis in rats. Tumor incidence and number are increased and latency is decreased in rats fed large amounts of corn oil, other polyunsaturated vegetable oils, or lard. Certain fats, e.g., rapeseed oil and beef fallow, have little or no effect. The influence of corn oil is exerted during promotion; lard appears to act both at initiation and during promotion. Mechanisms proposed for enhancement of carcinogenesis by dietary fat include alteration of endocrine balance and stimulation of cell division or changes in differentiation in the mammary gland. Data from studies of these postulated mechanisms are inconclusive; further investigation in well-defined animal models is needed. Colon carcinogenesis also is increased in rats fed high-fat diets in certain models, but in others there is no demonstrable effect of dietary fat. Interactions of fat and selenium, the requirement for which is governed by amount and type of dietary fat, may play a role in mammary gland and colon carcinogenesis. Lipotropic nutrients, required for normal fat metabolism, have powerful effects on hepatocarcinogenesis but have not been demonstrated to influence colon and mammary gland carcinogenesis. Lipotrope deficiency alters carcinogen metabolism, increases hepatocyte turnover, and accelerates induction of hyperplastic foci in the liver by many carcinogens. The significance of these abnormalities for carcinogenesis and the timing of the lipotrope effects are subjects of investigation in several animal models.
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PMID:Influence of dietary content of lipids and lipotropic nutrients on chemical carcinogenesis in rats. 618 51


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