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

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

Although there is general agreement that dietary calcium is protective against colon carcinogenesis, considerable controversy exists on the relative efficacy of the counterion in calcium supplements. We therefore conducted a comparative study in rats of four forms of calcium supplementation (calcium phosphate, casein, lactate, and a 50:50 phosphate-carbonate combination). The relative effects of these supplements on measurements of colon physiology, in vivo pH, fecal fat, individual bile acids, and in vivo cell proliferation were measured in the same animals. In contrast to results when amounts of calcium are varied, there was no effect of form of supplement on total fecal output or output of fecal fat. Calcium phosphate resulted in the most acidified cecal contents. Calcium phosphate and calcium casein resulted in lower fecal concentrations of lithocholate and lower amounts of total fecal bile acids than supplementation with the calcium lactate or combination diets. In addition, rats fed calcium phosphate had lower concentrations of fecal beta-muricholate than rats provided with the calcium combination supplement. In the proximal colon, calcium phosphate resulted in a significantly lower number of cells per crypt column and a lower labeling index than the calcium lactate diet. The position of the highest labeled cell was lower with calcium phosphate supplementation than with supplementation from the calcium combination or the calcium lactate diet. There was a highly significant correlation between the pH of cecal contents and labeling index in the proximal colon (r = 0.98, p = 0.003). The results suggest that calcium phosphate may inhibit colon tumor incidence more effectively than calcium lactate, because the calcium phosphate group had a lower colonic proliferative status than the calcium lactate group. Changes in the proliferative status of colonocytes are known to precede and accompany neoplasia.
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PMID:Calcium phosphate supplementation results in lower rat fecal bile acid concentrations and a more quiescent colonic cell proliferation pattern than does calcium lactate. 764 89

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

The impact of different dietary protein sources (whey, casein, soybean, red meat) on the incidence, burden and mass index of intestinal tumors induced by dimethylhydrazine in male Sprague-Dawley rats was assessed. A purified diet (based on AIN-76A) with a fat concentration of 20 g/100 g and other proteins substituted for casein (20 g/100 g) was used. Whey and casein diets were more protective against the development of intestinal tumors than were the red meat or soybean diets, as evidenced by a reduced incidence of rats affected (P = 0.15), fewer tumors per treatment group (burden, P < 0.005), and a reduced pooled area of tumors (tumor mass index) that formed (P = 0.39). Intracellular concentration of glutathione, an antioxidant and anticarcinogenic tripeptide, measured in liver, was greatest in whey protein- and casein-fed rats and lowest in soybean-fed animals (P < 0.001). For other tissues (spleen, colon, tumor) the differences were not significant, although the whey-fed animals had the highest concentrations of glutathione (P = 0.8). Whey is a source of precursors (cysteine-rich proteins) for glutathione synthesis and may be important in providing protection to the host by stimulating glutathione synthesis. A positive correlation was observed between mean fecal fat concentrations for rats in each treatment group and large intestinal tumor burden (r2 = 0.898, P = 0.05). Fecal fat could be involved in aiding initiation and/or promotion of carcinogenesis. Whatever the mechanism(s), dairy proteins, and whey proteins in particular, offer considerable protection to the host against dimethylhydrazine-induced tumors relative to the other protein sources examined.
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PMID:Dairy proteins protect against dimethylhydrazine-induced intestinal cancers in rats. 772 81

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.
Carcinogenesis 1995 May
PMID:Non-promoting effects of lean beef in the rat colon carcinogenesis model. 776 79

The purpose of this study was to determine if decreasing dietary protein from 24% (high protein) to 5% casein (low protein), substituting sucrose and cornstarch isocalorifically for casein, would modify the activity of protein kinase C (PKC) alpha and beta isoenzymes, as well as the expression of PKC alpha, beta, delta and zeta subtypes in the particulate, soluble and nuclear fractions of rat liver, and the development of gamma-glutamyltranspeptidase (GGT)-positive foci and nodules in the early stages (4, 7 and 60 days post-hepatectomy) of diethylnitrosamine-induced carcinogenesis promoted by 2-acetylaminofluorene in the diet plus partial hepatectomy (DEN-AAF-PH). In rats fed the 5% casein diet, body and liver weights decreased significantly compared with 24% casein-fed animals. However, the PKC total activity was unmodified. In 5% casein-fed rats, over-expression of PKC delta in the liver particulate fraction was detected at 7 and 60 days post-hepatectomy, with no significant PKC alpha and beta isoform activation. These animals showed only scattered GGT-positive hepatocytes at 60 days post-hepatectomy, with no appearance of hyperplastic foci or preneoplastic nodules. In contrast, rats fed the 24% casein diet demonstrated a progressive loss of PKC delta expression in the particulate fraction during tumour promotion, with activation and increased membrane association of PKC alpha and beta subtypes. These animals developed hyperplastic cell foci and preneoplastic nodules at 7 and 60 days respectively. Taken together, the results of this study suggest that overexpression of PKC delta in the liver particulate fraction of low protein-fed rats may play a specific role in inhibiting the development of hepatocellular focal lesions in the early stages of DEN-AAF-PH-induced carcinogenesis and confirm the role for nuclear PKC beta in promoting the selective growth of carcinogen-initiated hepatocytes in high protein-fed animals. No evidence for a role of PKC zeta in the carcinogenic process could be demonstrated.
Carcinogenesis 1995 May
PMID:Over-expression of protein kinase C delta is associated with a delay in preneoplastic lesion development in diethylnitrosamine-induced rat hepatocarcinogenesis. 776 90

There is a considerable variation in the diets used in studies on the influence of dietary fat on rat mammary cancer. In view of the fact that diet is the most remarkable factor in these studies, the aim of this work was to define two experimental diets, one of them normal (N3) and another hyperlipidic (HL20), both allowing the normal growth of the rat and neither of them containing factors that could unspecifically affect mammary carcinogenesis. Semisynthetic diets were selected instead of natural ones. A normal diet (3% corn oil, 18% casein, 67.9% dextrose) and a hyperlipidic diet (20% corn oil, 23% casein, 45.9% dextrose) were defined for the rat. Both diets also contain 5% cellulose, 5.9% salt mix and 0.24% vitamin mix. In order to avoid the influence of the above mentioned unspecific factors, the control of specificity and quality of nutrients is proposed as an essential measure. Moreover, it is also necessary to adopt measures to avoid the presence of fatty acid metabolites, including the calculation of the necessary vitamin E, selenium and sulfur amino acid and the determination of factors potentially able to stimulate or inhibit carcinogenesis such as phenolic antioxidants, retinoids or the trans isomer of fatty acids. On the other had, casein, dextrose, choline and folic acid contents were modified in order to equilibrate the lipid increase experimentally introduced in the HL20 diet or to ensure the normal maintenance of the animals' metabolism. The method used is based on the concept of quality assurance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental diets for the study of lipid influence on the induced mammary carcinoma in rats: I--Diet definition. 777 45

Matrilysin is believed to have a role in tumor progression. Its expression correlates with the occurrence of colorectal cancer. We have examined the expression of matrilysin mRNA in various colorectal disorders and its localization using RT-PCR and in situ hybridization. We have also examined whether Matrilysin is induced by cell to matrix interaction. Matrilysin mRNA was detected in all adenoma tissues examined, whereas none was detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis or normal colon tissues, and its message was localized in adenoma cells themselves. In addition, levels of enzyme activities of matrilysin were lower in adenomas compared with cancers in casein zymography. Matrilysin mRNA was induced by immobilized truncated fibronectin or RGD peptide. Thus, matrilysin may play an important role in colorectal carcinogenesis.
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PMID:Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin. 800 99

We have recently developed a mammary tumorigenesis system in which adult female BALB/c mice are grafted with two pituitaries from isologous donors and subsequently treated with a single i.v. injection of N-methyl-N-nitrosourea (MNU, 50 mg/kg). Mice bearing isografts have elevated serum titers of prolactin and progesterone which act on the mammary glands to produce a highly differentiated morphology resembling that of late pregnancy. MNU treatment of the mouse mammary gland in this differentiated state results in tumors in > 90% of tested animals. Since the mammary gland is believed to be particularly vulnerable to chemically induced carcinogenesis during alveolar morphogenesis, we chose to assess the susceptibility of the mammary gland during the initial weeks after pituitary isografting when they are ostensibly undergoing marked cell proliferation and differentiation. To this end, mice were isografted with pituitaries and subsequently analyzed at 1, 3, 5, 8 and 12 weeks for epithelial cell differentiation and susceptibility to MNU-induced tumorigenesis. By 3 weeks after isografting, the glands showed marked lobuloalveolar development and highest casein production. Tumor latency and frequency paralleled parenchymal differentiation for the first 3 weeks. By 5 weeks, and thereafter, the mice continued to be extremely susceptible to MNU-induced mammary carcinogenesis despite the highly differentiated state of the glands. Since tumors generated in this system are not dependent on pituitary isografts for their growth when transplanted to isologous recipients, and since the pituitary isograft does not act as a classical promoter but is required at the time of carcinogen treatment, we conclude that the pituitary isograft maintains a condition permissive for transformation to occur and a level of proliferation sufficient for the expression of the transformed phenotype.
Carcinogenesis 1994 Jul
PMID:Pituitary-isografted mice are highly susceptible to MNU-induced mammary carcinogenesis irrespective of the level of alveolar differentiation. 803 9

Inbred rat strains vary in their susceptibilities to mammary carcinogenesis. The Copenhagen (COP) and Wistar-Kyoto (WKY) rats are tumor resistant, whereas the Wistar-Furth (WF), Fischer (F344), and outbred Sprague-Dawley (SD) rats are susceptible. A dominant pattern of inheritance acting via the mammary carcinoma suppressor (Mcs) gene(s), which is mainly responsible for mammary tumor resistance, has been defined in the COP and WKY rats. In order to understand the basis of the phenotype, COP and WF mammary mRNAs were used for subtractive hybridization to isolate genes associated with the activity of the Mcs gene(s). Three genes, alpha-casein, lipoprotein lipase, and an unidentified gene, were found to be overexpressed in the mammary gland of the COP rat. In addition to alpha-casein overexpression, Northern analysis demonstrated that beta- and gamma-casein genes were also highly expressed in the mammary glands of tumor-resistant WKY and COP virgin rats but not the susceptible F344, WF, and SD strains. The association of casein gene expression with the tumor-resistant phenotype was further investigated by determining the functional site of the strain-specific casein gene regulation by using a mammary cell transplantation assay. In contrast to its normal endocrine control during pregnancy and lactation, casein gene overexpression was found to be controlled within the mammary epithelial cells of virgin rats. This is also the site of production and action of the Mcs gene product. Comparison of polymerase chain reaction-amplified beta-casein precursor RNA levels with the use of reverse transcription-polymerase chain reaction revealed that the regulation of this gene is likely at the transcriptional level. These data suggest an association of overexpression of casein genes, with the Mcs phenotype. The biological significance of this association is under investigation.
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PMID:Cloning and characterization of overexpressed genes in the mammary gland of rat strains carrying the mammary carcinoma suppressor (Mcs) gene. 824 34


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