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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The concept that diet plays an important role in the initiation and/or development of various types of tumors in man and experimental animals is well documented. The etiology of colon cancer is complex and multifactorial in nature, and there is little information on the dietary components that may act as initiators during colon tumorigenesis. We have evaluated various dietary heterocyclic mutagenic amines present in a typical "Western" diet for their nuclear damaging effect (presumably a genotoxic response) on the colonic epithelium of C57BL/6J mice in vivo. Among the mutagenic amines studied 2-amino-3,4-dimethylimidazo(4,5-f)quinoline and 2-amino-3-methylimidazo(4,5-f)quinoline were very potent inducers of nuclear aberrations. These observations provide us with clues that our daily diet may contain colon-specific genotoxic components. Promotional effects of dietary fat and/or bile acids on colon tumorigenesis have been well studied. Dietary levels of calcium (0.1, 0.5 or 1.0% by weight) appear to modify the toxicity of orally administered fat or cholic acid (assessed by quantifying cell proliferation). The colons of animals consuming 0.1% or 0.5% calcium diet were more susceptible to the toxicity, whereas the colons of those consuming a 1.0% calcium diet appeared more like control colons. These studies demonstrate a profound effect of dietary constituents on the pathobiology of the colonic epithelium which may have a marked influence on the colon tumorigenesis.
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PMID:Effect of dietary components on the pathobiology of colonic epithelium: possible relationship with colon tumorigenesis. 371 47

Epidemiological studies have shown an association between consumption of alcoholic beverages, particularly beer, and carcinoma of the large bowel, especially the rectum. We studied the effects of chronic dietary beer and ethanol consumption on experimental colonic carcinogenesis, fecal bile acid and neutral sterol levels, fecal bacterial flora, and colonic epithelial DNA synthesis. Ten-week-old male Fischer 344 rats were pair fed throughout the study with Lieber-DeCarli-type liquid diets providing comparable total carbohydrates, proteins, fats, and calories. The diets provided 23 or 12% of calories as alcohol in beer (Hi-Beer and Lo-Beer groups), 18 or 9% of calories as reagent ethanol (Hi-EtOH and Lo-EtOH groups), or no alcohol (control group). After 3 weeks of dietary acclimatization, 10 weekly s.c. injections of the bowel carcinogen azoxymethane, 7 mg/kg, were given (weeks 1-10). At necropsy in week 26, the high alcohol groups (Hi-Beer and Hi-EtOH) showed a significantly reduced incidence of tumors in the right colon (42 and 46% versus 81% in control, P less than 0.01 and P = 0.02) but no effect on left colonic tumorigenesis. By contrast, the low alcohol groups (Lo-Beer and Lo-EtOH) showed a trend toward increased incidence and proportion of tumors in the left colon (incidence of 42 and 35% versus 15% in control, P = 0.06 for Lo-Beer; 28 and 30% of tumors in left colon versus 11%, P = 0.08 and P = 0.07) but no effect on right colonic tumorigenesis. Numbers of right colonic tumors were inversely correlated with alcohol consumption of all rats (r = -0.350, P less than 0.001), but left colonic tumors were not correlated. Fecal bile acid and neutral sterol levels, fecal bacterial counts, and colonic epithelial DNA synthesis did not correlate with the effects of alcohol consumption on colonic tumorigenesis. Our findings suggest that: modulation of experimental colonic tumorigenesis by chronic dietary beer and ethanol consumption was due to alcohol rather than other beverage constituents; tumorigenesis in the right and left colon was affected differentially by the levels of alcohol consumption, reflecting complex interactions among the potential mechanisms for alcohol effects in the model used.
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PMID:Effects of chronic dietary beer and ethanol consumption on experimental colonic carcinogenesis by azoxymethane in rats. 381 56

Since the results of an earlier study indicating no effect of dietary fat on dimethylhydrazine (DMH)-induced colon cancer in rats differed from those of other investigators, the present study was initiated to determine if the modulating effect of fat intake on colon tumorigenesis was dependent on the route of DMH administration. Male weanling Sprague-Dawley rats (160) were fed one of two nutritionally balanced diets containing 5% or 24% corn oil (CO). Following 3 weeks adaptation to their respective diets, 40 rats from each diet group were treated with five doses of DMH (30 mg/kg) by intragastric (i.g.) gavage or subcutaneous (s.c.) injection, over a 3 week period. Rats were sacrificed when they showed clinical signs of colon tumor and surviving animals were killed 51 weeks after the initial DMH treatment. The cumulative probability of death with colon carcinoma did not differ between the dietary or treatment groups. There was no effect of route of administration or dietary fat on total intestinal tumor incidence. The number of rats with colon carcinoma was: 5% CO.IG = 25; 24% CO.IG = 27; 5% CO.SC = 23; 24% CO.SC = 19. Polypoid tumor incidence was significantly higher in the 24% CO.SC group (12/40) compared to the 5% CO.SC group (3/40) (Chi-squared = 5.25; p less than 0.03) while sessile tumor incidence was the inverse. Marginally significant differences in tumor morphology were noted between the IG groups.
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PMID:Interaction of dietary fat and route of carcinogen administration on 1,2-dimethylhydrazine-induced colon tumorigenesis in rats. 397 50

Early passage in vitro cultures of colorectal adenocarcinoma cells were used to determine if glucagon exerts a direct effect on growth of human colon cancer cells. Growth response assays indicated that glucagon generally stimulated growth between 2 and 10 micrograms/ml, with peak responses at 5 to 10 micrograms/ml. When glucagon-treated and control cultures were compared, 12 of the 14 cultures (86 percent) were stimulated by glucagon, with an increase in cells from 41 to 100 percent. The other two cultures did not respond to glucagon. These in vitro results suggest that glucagon may enhance growth of most colon cancer cells. Further studies on responsiveness to glucagon may help elucidate mechanisms of oncogenesis and suggest new therapeutic protocols for patients with colorectal cancer.
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PMID:Glucagon enhances growth of cultured human colorectal cancer cells in vitro. 407 59

A specific retinoic acid-binding protein (RABP) and a dihydrotestosterone-binding protein (DHTBP) appeared in colon tumors as well as in tissues surrounding the the tumors, but the proteins were nondetectable in normal adult human colon tissues. We have analyzed a total of 105 human colon tumors and related specimens for the presence of RABP and DHTBP as possible biochemical markers in colon tumorigenesis. The tissue or tumor extracts after incubation with (3H) retinoic acid or (3H) dihydrotestosterone were sedimented on sucrose gradients, and the binding proteins were detected from the 2S (RABP) or 6-7S (DHTBP) radioactive peaks. The overall results of the analysis illustrate that about 78% of the 74 human colon, rectum, cecum, and colorectum tumors analyzed contained RABP in detectable amounts. Thirty percent of the 20 colon tissues isolated from subjects suspected for colon cancer and 18% of the 11 normal colon tissues from autopsies contained detectable amounts of the binding protein. A comparative study on the quantitative amounts of RABP and DHTBP in colon tumors and related tissues indicates that the amount of retinoic acid or dihydrotestosterone bound per mg protein ranged from 0.8 to 5.1 pmoles in the binding protein-positive specimens. However, the relative amounts of the two binding proteins in these tissues were not in the same proportions. Appearance of RABP and/or DHTBP in the surrounding tissues of colon tumors correlated with the amounts of the binding protein(s) in the tumors. RABP of human colon tumor shared the same ligand specificity and other physicochemical characteristics as RABP of other species.
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PMID:Biochemical markers in colon tumorigenesis: retinoic acid and dihydrotestosterone-binding proteins. 629 60

Evidence that dietary fat has an influence on carcinogenesis comes from both epidemiological data and experiments with animals. The experimental studies have indicated that dietary fat acts primarily as a promoter of carcinogenesis and that the effect depends on the type as well as the amount of fat in the diet. Vegetable oils containing polyunsaturated fatty acids of the linoleic acid family (n-6) have been shown to enhance mammary tumorigenesis, but a fish oil containing polyunsaturated fatty acids of the linolenic acid family (n-3) had an inhibitory effect at higher levels of intake. These and other findings suggest that the effect may be related to prostaglandins or other biologically active products of polyunsaturated fatty acids. Epidemiological data show a positive correlation between dietary fat and mortality from cancer at various sites, and this is supported by results of animal experiments in the case of colon cancer and pancreatic cancer as well as breast cancer. In the epidemiological data, cancer mortality shows strong positive correlations with total dietary fat and with animal fat, but not with fat derived from plants. Fats and oils used as spreads, cooking fats, and salad oils are the main source of fat in the American diet. Other major sources are meats and dairy products. Fat intake could probably be reduced substantially without serious deleterious effects, and this might help to decrease the risk of developing certain types of cancer.
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PMID:Dietary fat and mammary carcinogenesis. 644 36

Experiments with animals and epidemiological data on human populations have provided evidence that high fat diets increase the incidence of certain types of cancer, such as breast cancer and colon cancer. High fat diets enhance mammary tumorigenesis in rats only when the fat contains a certain minimal level of essential fatty acids. Dietary fat appears to act as a promoter rather than affecting initiation of mammary tumors. It may do this by producing a more favorable environment for development and growth of tumor cells, either by changing the hormonal environment, by altering the properties of cell membranes thorugh changes in their lipid composition, or by other mechanisms, such as alterations in immune responses to tumor cells. The effect of dietary fat on colon cancer may be related to increased production and excretion of bile acids, some of which have been shown to be promoters of intestinal cancer in animals. It may be possible to utilize this knowledge of the effects of dietary fat on carcionogenesis to develop new methods for prevention and treatment of breast and colon cancer.
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PMID:Lipids and carcinogenesis. 699 9

Populations consuming diets high in fat and cholesterol exhibit a greater incidence of colon cancer than those consuming less fat and cholesterol. Lowering elevated serum cholesterol levels experimentally or clinically is associated with increased large-bowel tumorigenesis. Thus, cholesterol lost to the gut, either dietary or endogenously synthesized, appears to have a role in large-bowel cancer. Whether the effect(s) is mediated by increases in fecal bile acid excretion or some other mechanism is not clear.
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PMID:Cholesterol excretion and colon cancer. 726 Sep 37

Colon cancers commonly have allelic losses of chromosome 22q, which suggests the presence of a tumor suppressor gene on 22q. The candidate tumor suppressor gene on 22q is the neurofibromatosis 2 (NF2) gene. Using single strand conformation polymorphism (SSCP) analysis, we screened 24 pairs of colorectal cancer and adjacent normal mucosa, as well as 10 colon cancer cell lines from non-NF2 patients, for mutations in the coding sequence of the NF2 gene. Two SSCP variants, one in exon 14 and another one in exon 16, were detected in two of the sporadic colorectal cancers, but not in adjacent normal mucosa samples. Sequencing of these variants in one tumor detected an A-to-G transition in bp 1459 of the NF2 cDNA, resulting in the change of Ile to Val at codon 487 of merlin, the NF2 protein product. The other tumor showed a 2-bp (CT) deletion in the intronic sequence of the alternatively spliced exon 16. These results suggest that the NF2 gene is probably involved in some colorectal tumors, but is not the critical chromosome 22q tumor suppressor gene involved in colon tumorigenesis.
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PMID:Neurofibromatosis 2 gene in human colorectal cancer. 749 38


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