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

The role which the human colon fulfils in digestion and metabolism remains largely undocumented. Its capacity to conserve water and electrolytes is well known although how this is controlled is uncertain. In the animal kingdom, calcium and magnesium absorption from the colon are improtant as are absorption and synthesis of vitamins. The abundant microflora of the human colon gives it unique properties. Dietary residue is metabolised forming short-chain fatty acids, hydrogen, carbon dioxide and methane; whilst 20% of urea synthesised in man is broken down in the colon to ammonia, which is reabsorbed, and carbonic acid. The microflora also degrades a wide variety of organic compounds including food additives, drugs, bile salts, and cholesterol which may be relevant to the development of colon cancer. Regional differences in colonic function also exist making interpretation of data from this relatively inaccessible organ more difficult.
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PMID:The colon: Absorptive, seccretory and metabolic functions. 120 9

Orotic acid, first discovered in ruminant milk, is an intermediate in the pyrimidine biosynthesis pathway of animal cells. Its synthesis is initiated by the formation of carbamoyl phosphate (CP) in the cytoplasm, with ammonia derived from glutamine. Ureotelic species also form CP in the first step of urea synthesis in liver mitochondria. For that, ammonia is derived from tissue fluid. When there is insufficient capacity for detoxifying the load of ammonia presented for urea synthesis, CP leaves the mitochondria and enters the pyrimidine pathway, where orotic acid biosynthesis is stimulated, orotic acid excretion in urine then increases. Orotic acid synthesis is abnormally high with hereditary deficiencies of urea-cycle enzymes or uridine monophosphate synthase. It is also elevated by ammonia intoxication and during feeding of diets high in protein, high in lysine with respect to arginine, or deficient in arginine, ornithine, and citrulline. Rats fed 1% orotic acid or diets deficient in urea-cycle amino acids develop fatty livers, which has not been demonstrated in other species. Humans consuming 6 g of orotic acid daily have not shown adverse effects. Rats fed 1% orotic acid or arginine-deficient diets also showed more and larger foci positive for gamma-glutamyl transpeptidase and more liver tumors after administration of carcinogens and partial hepatectomy. Orotic acid feeding was also associated with the tendency for development of larger mammary tumors induced by chemical carcinogens in rats and with development of urinary bladder calculi containing high concentrations of orotic acid in mice. Conditions that raise tissue orotic acid change purine-pyrimidine ratios. It is unknown whether tissue orotate concentrations play a role in the recently observed enhanced proliferation of cells in the colon of rats fed high-protein, high-fat diets or in the promotion of chemically induced colon cancer by intrarectal administration of ammonium acetate.
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PMID:Nitrogen-stimulated orotic acid synthesis and nucleotide imbalance. 154 44

Epidemiological data from different populations have suggested positive relationships between the incidence of colon cancer and meat and fat intake and a negative relationship with dietary fiber consumption. Within population comparisons have been less clearcut. Current theories on colonic carcinogenesis in man involve increased concentrations of bile acids and their metabolites, alterations in colonic pH, low Ca++, raised NH3 and long chain fatty acid levels, and alterations in bacterial numbers, type, and metabolic capabilities. The many laboratory studies in rats have been difficult to interpret since powerful initiators of carcinogenesis are always required and this rather than the promotion of spontaneous neoplastic change is the sine qua non for tumor growth in this situation. The current dilemma highlights the lack of knowledge of most aspects of human colonic physiology. Until these issues are more clearly resolved the epidemiological leads would point to low fat diets rich in less processed starchy foods with increased fiber as possible protection. Such advice is in common with the pronouncements of heart foundations, diabetes associations, and recommendations of official bodies to the general public.
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PMID:Cancer risk: possible protective role of high carbohydrate high fiber diets. 302 Sep 71

Dietary cooked casein promotes colon cancer in rats. We speculated and tested the hypothesis that cooking reduces the digestibility of casein, and increases the yield of bacterial metabolites, which are potential promoters of cancer. We investigated dietary means to manipulate nitrogen transfer and fermentation in the caecum. The caecal digestion of casein (cooked or not), keratin (hydrolysed or not) and bovine serum albumin (oxidized or not) was measured in rats. Protein fermentation was estimated by assaying caecal ammonia and branched-chain fatty acids. Keratin and cooked casein were digested to a very low extent, and were poorly fermented. Rats given cooked casein had 2-3 times more ammonia in their caecum than animals given the other proteins. Antibiotics (bacitracin, chlortetracycline, neomycin and spiramycin, at either 20 and 80 micrograms/ml water) decreased caecal ammonia in rats eating cooked casein, with spiramycin being most efficient. These data support the hypothesis given above, and provide ways to manipulate caecal ammonia.
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PMID:Digestion and fermentation of proteins in rats fed keratin, albumin, cooked casein and antibiotics. 751 Apr 93

Thermolyzed casein is known to promote the growth of aberrant crypt foci (ACF) and colon cancer when it is fed to rats that have been initiated with azoxymethane. We speculated that the promotion was a consequence of increased colonic protein fermentation (i.e., that the thermolysis of the casein decreases its digestibility, increases the amount of protein reaching the colon, and increases colonic protein fermentation and that the potentially toxic products of this fermentation promote colon carcinogenesis). We found that the thermolysis of casein reduces its digestibility and increases colonic protein fermentation, as assessed by fecal ammonium and urinary phenol, cresol, and indol-3-ol. Thermolysis of two other proteins, soy and egg white protein, also increases colonic protein fermentation with increased fecal ammonia and urinary phenols, and thermolysis of all three proteins increases the levels of ammonia and butyric, valeric, and i-valeric acids in the cecal contents. We found, however, that the increased protein fermentation observed with thermolysis is not associated with promotion of colon carcinogenesis. With casein, the kinetics of protein fermentation with increasing thermolysis time are clearly different from the kinetics of promotion of ACF growth. The formation of the fermentation products was highest when the protein was thermolyzed for one hour, whereas promotion was highest for protein that had been thermolyzed for two or more hours. With soy and egg white, thermolysis increased colonic protein fermentation but did not promote colon carcinogenesis. Thus, although thermolysis of dietary casein increases colonic protein fermentation, products of this fermentation do not appear to be responsible for the promotion of colon carcinogenesis. Indeed, the results suggest that protein fermentation products do not play an important role in colon cancer promotion.
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PMID:Colonic protein fermentation and promotion of colon carcinogenesis by thermolyzed casein. 760 87

A high-fat/high-protein diet has been reported to promote colon cancer by increasing luminal bile acid and ammonia concentrations, whereas butyrate, calcium, and low colonic pH may have protective effects. In this study, bromodeoxyuridine labeling of colonic epithelium was investigated after incubating biopsies from the ascending colon of 70 patients with HCl (20 mM, pH 6.0), butyric acid (H-BUT, 20 mM, pH 6.0), sodium butyrate (Na-BUT, 10 mM, pH 8.0), CaCl2 (10 mM), calcium butyrate (Ca-BUT, 10 mM), ammonium butyrate (NH4-BUT, 10 mM), deoxycholic acid (DCA, 5 microM), and a combination of DCA and Na-BUT (DCA/Na-BUT, 5 microM/10 mM). Compared to NaCl, H-BUT and Na-BUT increased the whole crypt-labeling index significantly, whereas HCl and CaCl2 had no effect. Reduced labeling, however, occurred with Ca-BUT in comparison to equimolar Na-BUT. No differences in the labeling indexes were found for NH4-BUT compared to Na-BUT, but increased labeling with expansion of the proliferative zone to the upper 40% of the crypt was seen with DCA compared to NaCl. DCA-induced hyperproliferation was abolished by coincubation with DCA/Na-BUT. These data suggest that butyrate, calcium, and DCA have complex influences on mucosal proliferation. Since luminal concentrations of these compounds are influenced by dietary interventions, the findings of this study may be of particular interest with regard to colon cancer development and prevention.
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PMID:Proliferation of human colonic mucosa as an intermediate biomarker of carcinogenesis: effects of butyrate, deoxycholate, calcium, ammonia, and pH. 832 39

Formulated diets associated with a high risk (HR) or low risk (LR) for colon cancer were used to assess the effect of diet on putative metabolic biomarkers in human flora-associated rats: The HR diet was high in fat and sucrose and low in calcium and fiber; the LR diet was low in fat and high in starch, calcium, and fiber. The nutrient-to-energy ratio and energy intake were the same for both diets. Body and liver weights were significantly higher in animals fed the HR diet, possibly due to greater energy availability from fat. Cecal weights were significantly higher in animals fed the LR diet, presumably due to a bulking effect of the fiber and increased bacterial biomass. The HR diet significantly altered cecal bacterial enzyme activity: beta-glucuronidase activity increased 2.5-fold, and beta-glucosidase activity was halved. Ammonia production and the bacterial metabolism of 2-amino-3-methyl-7H-imidazo[4,5-f] quinoline (IQ) to 7-hydroxy-IQ (7OHIQ) were significantly higher in animals fed the HR diet. The HR diet, which contained factors common to diets consumed throughout the Western world, increased beta-glucuronidase activity, elevated cecal ammonia concentrations, and enhanced the genotoxic risk from 7OHIQ formation, three putative metabolic biomarkers of colorectal cancer. The significance of the reduction in beta-glucosidase is unclear.
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PMID:Effects of high- and low-risk diets on gut microflora-associated biomarkers of colon cancer in human flora-associated rats. 910 54

In a randomized, crossover dietary intervention study, 12 Australians (of white descent) consumed a diet typical of low-income communities in China and an average Australian diet so that effects on fecal markers thought to be relevant to colon cancer risk could be compared. The Chinese diet contained 35.3 g starch/MJ daily [including 2 g resistant starch (RS)/MJ and 1.5 g nonstarch polysaccharides (NSPs)/MJ]; the Australian diet contained 12 g starch/MJ daily (including 0.8 g RS and 2.7 g NSPs/MJ). Subjects followed each diet for 3 wk. Serum cholesterol concentrations were significantly lower after the low-fat, high-starch Chinese diet than after the Australian diet (mean +/- SEM: 4.17 +/- 0.30 compared with 5.04 +/- 0.28 mmol/L, respectively, P < 0.05), a difference indicative of dietary compliance. Fecal pH was lower after the Chinese diet (6.51 +/- 0.04) than after the Australian diet (6.63 +/- 0.05; P < 0.05). For all other fecal markers examined, however, the Chinese diet produced less favorable changes, including lower fecal bulk (86 +/- 11 compared with 141 +/- 20 g wet wt/d, P < 0.01), slower transit through the gut (69 +/- 6 compared with 56 +/- 7 h, P = 0.06), lower fecal concentrations of short-chain fatty acids [72.8 +/- 7.3 compared with 98 +/- 7.6 mmol/L (including butyrate: 12.2 +/- 1.3 compared with 18.4 +/- 2.3 mmol/L), P < 0.05], and higher fecal concentrations of potentially damaging ammonia (540 +/- 50 compared with 450 +/- 40 mg/L, P < 0.01) and phenols (109.2 +/- 13.2 compared with 68.5 +/- 12.9 mg/L, P < 0.01). These results suggest that consumption of a high-starch diet alone is insufficient to reduce the risk of developing colon cancer.
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PMID:Modulation of fecal markers relevant to colon cancer risk: a high-starch Chinese diet did not generate expected beneficial changes relative to a Western-type diet. 970 Nov 96

Ammonia is present at high concentration in the colon lumen and is considered a colon cancer suspect. Furthermore, ammonia usually eliminated by the liver in the ornithine cycle is considered highly toxic to cerebral function when present in excess in the blood plasma. Therefore, the metabolic pathways involved in ammonia metabolism in colonocytes were studied in the present study. Rat colonocytes were found equipped with low carbamoylphosphate synthase I activity, high ornithine carbamoyltransferase and arginase activities and low argininosuccinate synthase activity. High (10 and 50 mmol/l) NH4Cl concentrations but not low concentrations (1 and 5 mmol/l) were found able to increase respectively 3- and 10-fold the conversion of radioactive L-arginine to L-citrulline. In contrast, very low capacity for L-citrulline conversion to L-arginine is found in colonocytes. It is concluded that an incomplete ornithine cycle is operative in colonocytes which results in ammonia stimulated L-citrulline production. The contribution of this metabolic pathway in relation to ammonia detoxication by colonocytes is discussed.
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PMID:Metabolic capacity for L-citrulline synthesis from ammonia in rat isolated colonocytes. 1035 Jun 56

Up to 80% of breast, bowel and prostate cancers are attributed to dietary practices, and international comparisons show strong positive associations with meat consumption. Estimates of relative risk obtained from cohort investigations are in the same direction, although generally weak, and red and processed meats rather than white meat seem to be associated with elevated risk of colon cancer. In breast cancer, there are consistent associations with total meat intake and there is evidence of a dose response. Despite these associations with meat, existing studies suggest that vegetarians do not have reduced risk of breast, bowel or prostate cancer, but there are no quantitative estimates of amounts of meat consumed by meat eaters in these cohort studies. Possible mechanisms underlying epidemiological associations include the formation of heterocyclic amines in meat when it is cooked. These heterocyclic amines require acetylation by P450 enzymes, and individuals with the fast-acetylating genotype who eat high amounts of meat may be at increased risk of large-bowel cancer. NH3 and N-nitroso compounds (NOC) formed from residues by bacteria in the large bowel and probably also important. NH3 is a promotor of large-bowel tumours chemically induced by NOC, and some of the chromosomal mutations found in human colo-rectal cancer are consistent with effects of NOC and heterocyclic amines. However, the type, amount, and cooking method of meat or protein associated with increased risk are not certain. The effects of high levels of meat on NH3 and NOC output are not reduced by increasing the amount of fermentable carbohydrate in the diet, but interaction between meat, NSP and vegetable intakes on the risk of cancer has not been studied comprehensively. The interaction between dietary low-penetrance genetic polymorphic and somatic mutation factors has also been investigated to a limited extent. Current Department of Health (1998) recommendations are that meat consumption should not rise, and that consumers at the top end of the distribution should consider a reduction in intakes.
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PMID:High-meat diets and cancer risk. 1046 62


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