Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effect of cooked food components on the promotion of microadenoma growth in the colons of mice and rats. CF1 mice and Fisher 344 rats were initiated with azoxymethane, with 152 mice receiving four weekly i.p. injections of 5 mg/kg, 59 rats receiving a single injection of 20 mg/kg, and 24 rats receiving 30 mg/kg. A week after the last injection, the animals were randomly assigned to one of eight diets with identical ingredients, but the three components, sucrose, casein, and beef tallow, either uncooked or cooked. Control animals were given diets with uncooked ingredients. Experimental animals were fed diets in which one, two, or three of the components were cooked in an oven at 180 degrees C until golden brown before they were added to the diet. After 100 days on the diets, the colons were fixed, stained with methylene blue, and scored for microadenomas. The mice and the rats fed cooked sucrose, or casein and beef tallow cooked together, had three to five times more large microadenomas than did the controls (P ranging from 0.02 to 0.0001). No significant increase was observed with the five other cooked diets. Two rats fed the casein and beef tallow cooked together had adenocarcinomas. Thus, a diet containing 20% of cooked sucrose, or 40% of casein and beef tallow cooked together, promotes the growth of colonic microadenomas in initiated mice and rats, and would appear to contain promoters for colon cancer.
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PMID:Promotion of colonic microadenoma growth in mice and rats fed cooked sugar or cooked casein and fat. 220 61

The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent and cAMP-independent kinase activities were measured in the 1,2-dimethylhydrazine (DMH) induced rat colon cancer and in untreated colon. Previous studies had shown that intestinal tumors induced by chronic exposure to DMH contained 2-fold less intracellular cAMP. The present findings indicate that reduction in cAMP-dependent protein kinase activities also occur in colon cancer cells. Similar hydrogen ion dependence (pH 6-7) and approximate association constants (Ka approximately 0.1 microM) were observed for the enzymes existing in both normal and tumor tissues, while the cAMP-dependent tumor protein kinase was found to phosphorylate phosvitin and casein to a greater degree. These recent findings are consistent with the concept that the concentrations of cAMP and activities of its associated enzyme system are inversely related to the cell proliferation state.
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PMID:Adenosine 3',5'-cyclic monophosphate dependent and independent protein kinase activities in 1,2-dimethylhydrazine induced rat colon cancer. 628 71

In the United States, colon cancer is the most common form of internal cancer in both sexes. Prevention of the disease depends on early diagnosis of polyps or pre-cancerous lesions. The response of normal human colon fibroblasts ( CRL1459 ) was used to identify individuals with clinical pre-cancer. Their plasma induced transformation associated morphology characterized by the retraction of cellular processes, cell rounding and eventual detachment from the vessel surface. Those plasma samples which induced a transformation associated morphology contained significantly increased levels of protease as shown by casein hydrolysis (Bio-Rad, CA). We are using hyperproteinasemia as a biomarker to identify individuals with polyps who have hereditary adenomatosis of the colon and rectum (ACR). We are currently evaluating cell cultures versus biochemical assays as a means for early detection of precancerous tumors in the general population. The findings of a tumor associated protease in clinical precancer, and its effect on cell cultures support our proposal that protease activity promotes tumor progression in ACR and may represent the gene defect in this hereditary disease.
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PMID:Use of cell culture to identify human precancer. 637 4

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

The present study was undertaken to investigate certain dietary factors known to affect the development of colon cancer for their ability to modulate aberrant crypt foci (ACF). Male Wistar rats were initiated with oral doses of dimethylhydrazine dihydrochloride (DMH-2HCl, 20 mg/kg body wt) once a week for 10 or 20 weeks. Throughout the study the animals were fed 1) semisynthetic casein-based control diet, 2) control diet with 20% lard, 3) control diet with 20% lard and 20% dietary fiber, or 4) control diet where most of the carbohydrate pool was substituted with sucrose and dextrin. The composition of the different diets was designed to achieve equivalent intakes of essential nutrients. Animals were killed after 10, 20 and 31 weeks. The study showed a pronounced effect of dietary composition on the development of DMH-induced ACF. The diet high in sucrose and dextrin caused a statistically significant increase (p < or = 0.05) in the total number of ACF and number of small and medium ACF. Adding lard to the standard diet did not cause an increase in ACF, but if the dietary fiber was added to the high-fat diet, a statistically significant reduction (p < or = 0.05) in the total number of ACF and number of small and medium ACF was observed. The values of large and extra-large foci reflected the same effect of diets on ACF. The results indicate that tumors in the group fed the diet high in refined carbohydrates were more prominent and occurred with a higher incidence. However, the difference is based on few tumors and is not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of different diets on development of DMH-induced aberrant crypt foci and colon tumor incidence in Wistar rats. 764 84

We have used the aberrant crypt focus (ACF) assay to test and develop hypotheses linking diet and colon cancer. The hypotheses were suggested by epidemiological studies that identified possible dietary factors associated with colorectal cancer risk. The ACF assay was used to quantitate the effect of the dietary factors on the initiation and growth of these putative precursors of colon cancers in experimental animals. Using this approach we have developed 3 new hypotheses for the role of diet in colorectal cancer. These are (1) a risk associated with 5-hydroxymethyl-2-furaldehyde in caramelized sugar, (2) a risk associated with some factor in thermolyzed casein, and (3) a risk associated with single nutrient boluses of sucrose and fructose. The importance of these hypotheses has still to be tested in long term carcinogenesis experiments, in analytic epidemiology studies and then, perhaps, in intervention trials.
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PMID:Diet, aberrant crypt foci and colorectal cancer. 769 90

Recent epidemiologic studies have implicated red meat consumption as a risk factor for colon cancer in both men and women. However, it has been very difficult to separate the effects of meat as a protein source from the accompanying fat content of the diets analyzed in these studies. Experimental data from rodent feeding trials show mixed results, with no firm conclusions being possible in terms of the colon-cancer promoting effects of meat fat. The goal of the present study was to compare, in an experimental animal model, the effects of beef with casein as a protein source, within the context of a low- and high-fat diet containing either corn oil or beef tallow, on promotion of colon carcinogenesis. Tumors were induced in Sprague-Dawley rats with 1,2-dimethylhydrazine (20 mg/kg body wt for 10 weeks). Two hundred and eighty male weanling rats were randomized to eight dietary treatment groups of a 2x2x2 factorial design with fat source (corn oil vs. beef tallow), fat level (5% vs. 20%), and protein source (very lean beef vs. casein) as the factors. Diets were fed ad libitum before, during and after carcinogen treatment for a total of 27 weeks. At termination of the study, animals were examined for location, size and type of colon or extracolonic lesions. The total incidence and number of colon tumors were significantly lower in the groups fed beef rather than casein. High fat levels, regardless of source, significantly increased the number of colon adenomas. These results demonstrate that when lean beef is used as the protein source in the context of a low-fat diet, fewer intestinal tumors develop. These data do not support the belief that red meat consumption increases the risk for colon carcinogenesis, but underscores the importance of fat level in dietary context.
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PMID:Non-promoting effects of lean beef in the rat colon carcinogenesis model. 776 79

Consumption of fermented dairy foods has been linked to reduced incidence of colon cancer in population groups. Recently, biologically active compounds have been isolated from these products. Bacterial proteinases, produced by dairy starter cultures, generate a variety of peptides from casein. Some of these casein-derived peptides are likely to alter intestinal cell kinetics. Effects on colon cell kinetics because of the presence of casein-derived peptides may be a mechanism through which fermented dairy foods reduce the risk of colon cancer. We have used two intestinal cell lines (IEC-6 cells, derived from normal rat intestine, and Caco-2 cells, derived from human colon adenocarcinoma) to identify casein peptides that affect intestinal cell kinetics. Cell culture media containing casein were inoculated with three commercial starter cultures and incubated for 4, 8, or 24 h. The bacteria-conditioned media were then filter-sterilized and incubated with the intestinal cells for 6 or 24 h. Rates of [3H]thymidine incorporation and cell cycle kinetics determined by flow cytometry were affected by the culture-modified media in both cell lines. The IEC-6 cells tended to reduce, and Caco-2 cells to increase, rates of cell division after exposure to the media. Intestinal cell response varied among the starter cultures. The results support the use of intestinal cell cultures to identify casein peptides generated by dairy starter cultures, which affect intestinal cell kinetics.
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PMID:A cell culture model to identify biologically active peptides generated by bacterial hydrolysis of casein. 804 61

Dietary casein cooked at 180 degrees C promotes the growth of aberrant crypt foci and colon cancer in rats initiated with azoxymethane. We speculated that promotion was due to a product that could be extracted by a solvent, such as 5-hydroxymethyl-2-furaldehyde (HMF), with tumor- promoting activity or the carcinogenic heterocyclic aromatic amines (HAA). This hypothesis was tested by extracting cooked casein with solvents and water. The extracts were then 1) assayed by high-performance liquid chromatography for HMF and HAA, 2) measured for mutagenicity on a frame-shift-sensitive strain of Salmonella typhimurium, and 3) fed for 100 days to azoxymethane-initiated rats to test the promoting effect on aberrant crypt foci. Data show that 1) no HMF or HAA was detected in cooked casein, 2) no mutagenicity was detected on strain TA98, with or without metabolic activation, and 3) promotion was not associated with the extracts but with the cooked casein residue. Therefore the promotion by cooked casein would not appear to be associated with a product that can be extracted by solvents.
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PMID:Lack of aberrant crypt promotion and of mutagenicity in extracts of cooked casein, a colon cancer-promoting food. 861 44


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