Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

6-(p-Dimethylaminophenylazo)benzothiazole (6BT) and 5-(p-dimethylaminophenylazo)indazole (5I) comprise respectively a carcinogen/non-carcinogen pair of monoazo dyes related to the hepatocarcinogen, butter yellow (DAB). While both members of the pair are potent bacterial mutagens in vitro, only 6BT induces unscheduled DNA synthesis in rat liver in vivo. To investigate factors responsible for these divergent activities we have determined in rats: relative rates of uptake from the gut after direct injection of 14C-labelled compound into intestine in situ, and after administration p.o.; distribution in selected tissues and elimination in urine, faeces and bile; binding of both compounds in vivo to liver DNA. The results revealed that, although 5I was taken up from the gut to a lesser extent than 6BT, comparable labelling associated with both compounds was detected in the presumed target organ (the liver). 5I binds in vivo to DNA much less effectively than 6BT. Therefore it would seem that other factors, such as differential metabolism in vivo, are more important than differences in uptake and distribution in accounting for the divergent activities of 6BT and 5I.
Carcinogenesis 1986 Jun
PMID:The disposition and in vivo covalent binding to liver DNA of the monoazodyes 6-(p-dimethylaminophenylazo)benzothiazole (6BT) and 5-(p-dimethylaminophenylazo)indazole (5I) after administration to the rat. 308 65

Secondary bile acids have been implicated in colonic carcinogenesis. Transformation of primary into secondary bile acids (7 alpha-dehydroxylation) in the large bowel is a pH-dependent process. Inhibition of this reaction could be achieved by lowering colonic pH. We, therefore, studied the effects of lactulose (a non-absorbable disaccharide), which is capable of acidifying colonic contents, on secondary bile acid metabolism. Because this metabolism is age dependent, lactulose was given (0.3 g kg-1 twice daily for 12 weeks) to nine middle-aged (age 31-54 years; mean 45.7) and ten elderly subjects (age 56-81 years; mean 66.4). Twice before, and after 6 and 12 weeks' lactulose administration, biliary and faecal bile acids, whole gut transit time, faecal weight and dry weight, and faecal pH were recorded. The concentration of (iso)lithocholic and deoxycholic acid in faeces was higher in elderly subjects (P less than 0.05) but the excretion was comparable. After lactulose the concentration and excretion of the major secondary bile acids decreased. The primary bile acid fraction rose from 5% before, to more than 20% after, lactulose (P less than 0.05). Faecal weight increased and faecal dry weight decreased, resulting in a higher faecal water output during lactulose. Whole gut transit time did not change. The faecal pH dropped after 6 (P less than 0.05) and further after 12 weeks' lactulose (P less than 0.05). The percentage deoxycholic acid in bile was higher, and cholic acid lower, in elderly subjects (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of secondary bile acid formation in the large intestine by lactulose in healthy subjects of two different age groups. 313 Feb 60

Radiotracer methods were used to determine the distribution of 3-methylcholanthrene (3-MC) within the lymphoid organs of rats following i.g. intubation, i.l. injection into the small intestine, i.v. injection or direct injection of the Peyer's patches with 3-[6-14C]methylcholanthrene (14C-MC). The data indicate that the gut-associated Peyer's patches and mesenteric lymph nodes were exposed to higher amounts of orally administered 14C-MC than any of the other lymphoid organs. Whereas the Peyer's patches exhibited the highest sp. act. for longer periods of time when low amounts of 14C-MC were administered, the sp. act. of the mesenteric lymph node were greater when rats were intubated with higher amounts of 14C-MC. Furthermore, the Peyer's patches were exposed to higher amounts of possible metabolites of 14C-MC. Injection of 14C-MC into the small intestinal lumen resulted in increased ratios of the Peyer's patch sp. act. to mesenteric lymph node sp. act., indicating that by-passing the stomach altered the distribution patterns. Data from rats injected i.v. with 14C-MC demonstrated that mesenteric lymph nodes but not Peyer's patches adsorbed and retained 14C-MC from the blood and indicated that the 14C-MC associated with Peyer's patches of i.g. treated rats was adsorbed from the gut rather than from the blood. Results obtained from rats which were exposed to 3-MC by directly injecting Peyer's patches with 14C-MC also indicated that the Peyer's patches were able to retain 3-MC once localized within this lymphoid organ, to metabolize the 3-MC and to possibly excrete the polycyclic aromatic hydrocarbon into the small intestine. Collectively the data indicate that Peyer's patches have an important role in the adsorption from the gut and subsequent retention of 3-MC and hence may be a likely target organ for lymphoid carcinogenesis following oral exposure to carcinogenic polycyclic aromatic hydrocarbons.
Carcinogenesis 1986 Aug
PMID:The role of the Peyer's patch in carcinogenesis. I. The adsorption from the gut and retention of 3-methylcholanthrene by Peyer's patches. 373 79

The heterocyclic amine 3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole (Trp-P-1) was administered as a single oral dose to conventional, bile-fistulated and germ-free rats. There was rapid excretion of Trp-P-1 and its metabolites via the bile, urine and feces. The pattern of metabolites did not differ markedly between the three excretory routes. While there was considerable excretion of unmetabolized Trp-P-1, at the dose level used, there was also extensive metabolism to primary ring-hydroxylated and N-acetylated metabolites which were polar enough to be excreted without undergoing conjugation reactions. Four of the metabolites exhibited mutagenic activity towards Salmonella typhimurium TA98 in the presence of S9 mix. However, all showed a lower mutagenicity than the parent compound. Studies with the bile-fistulated animals indicated that enterohepatic circulation was occurring with Trp-P-1. The intestinal microflora did not appear to have a major role to play in the metabolism of this heterocyclic amine but they did lead to the formation of 'bound fecal residues' in the gut of the conventional animals.
Carcinogenesis 1986 Aug
PMID:Metabolism of the dietary carcinogen TRP-P-1 in rats. 373 83

Strains of intestinal bacteria were capable of deconjugating benzo[a]pyrene metabolites in vitro. The hydrolysis products, and other primary oxidative metabolites of benzo[a]pyrene, were stable to further degradation by the strains tested. Cytochromes P-450 and b5 were detectable in the mucosa of the guinea-pig small intestine, but not in the mucosae of the colon or rectum. The concentrations were unaltered by administration of benzo[a]pyrene and/or the feeding of high-fat or high-cholesterol diets. Benzo[a]pyrene hydroxylase was measurable in the mucosa of the upper intestine, but was present in the lower gut only at very low levels in some animals. The activity was inducible, by oral administration of benzo[a]pyrene, in the small intestinal mucosa of guinea-pigs fed normal diet but not in those fed high-fat and high-cholesterol diets. Low levels of covalent binding of 3H to DNA of liver and gut mucosa were obtained in guinea-pigs dosed orally with 3H-benzo[a]pyrene. Comparison with data for animals given 3H2O suggested that approx. one quarter of the binding was probably due to 3H exchange during metabolism. The feeding of high-fat and high-cholesterol diets did not increase this binding. Guinea-pigs fed high-fat and high-cholesterol diets excreted a greater proportion of an oral dose of 3H-benzo[a]pyrene in urine, and less in faeces than animals fed a normal diet. Due to the low, and apparently non-inducible, levels of benzo[a]pyrene hydroxylase activity and of covalent binding in the colonic mucosa, the administration of benzo[a]pyrene to guinea-pigs fed high-fat or high-cholesterol diets appears unlikely to provide a novel animal model for studies on mechanisms of colon carcinogenesis.
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PMID:The intestinal metabolism and DNA binding of benzo[a]pyrene in guinea-pigs fed normal, high-fat and high-cholesterol diets. 375 Nov 11

Changing numbers of mast cells were observed in precancerous and cancerous lesions of the gut in mice treated by 1, 2-dimethylhydrazine dihydrochloride. The study included 18 samples of abnormal and atypical epithelium, 14 samples of preinvasive carcinoma, 15 samples of infiltrative carcinoma, and 12 control samples from untreated mice. Carcinogenesis was accompanied by a significant increase of mast cell numbers culminating in preinvasive carcinoma. A decrease of mast cells followed in fully developed adenocarcinomas up to numbers comparable to but more variable than those found in abnormal and atypical epithelium.
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PMID:[Mastocytes in the process of cancerogenesis. I. Study of experimental model systems]. 379 52

The urinary excretion of N-nitroso-L-[U-14C]proline by conventional microflora and germ free rats was used to assess the role of the gut bacteria and oral nitrate in the endogenous formation of N-nitroso compounds. The formation of nitrosoproline was qualitatively similar in conventional and germfree rats (equivalent to nitrosation of approximately 0.01-0.05% of the initial dose of [U-14C]proline) suggesting no involvement of the intestinal flora in this reaction. Furthermore, nitrosamino acid production was similar following the administration of nitrate and [U-14C]proline or [U-14C]proline alone, demonstrating no involvement of exogenous nitrate under the conditions of the experiment. Dietary contamination with nitrate/nitrite was negligible. The results are consistent with the suggestion that nitrate/nitrite reserves in the body are important in the formation of nitrosoproline in vivo.
Carcinogenesis 1985 Nov
PMID:The role of oral nitrate in the nitrosation of [14C]proline by conventional microflora and germ-free rats. 405 79

This paper reviews recent research on the characterization, properties, and definition of dietary fiber as well as its possible role in colonic carcinogenesis and diverticulosis. Despite progress in analytic methods and characterization, an accepted definition and terminology for fiber are lacking as is an accurate, rapid method for measurement of total dietary fiber or fiber in foods. Mechanisms of effects of fiber in the gut and the significant of interactions between fiber, nutrients gut flora and associated metabolites, and enteric secretions are unclear. Epidemiologic and experimental data indicate an increased risk of diverticular disease and colonic cancer with low-fiber intakes; however, genetic, environmental, cultural, dietary, and other variables were often uncontrolled in the epidemiologic studies. Thus, conclusive evidence for a causal relationship between low intake of fiber and diverticulosis or colonic cancer is not available, and the question whether first protects against human colonic cancer and/or diverticulosis is not completely resolved. Clinical trials in which symptomatic diverticular disease was treated with supplementary dietary fiber have generally had favorable results. Numerous specific questions require additional study before a role for dietary fiber in the prevention of human colonic diverticulosis and cancer of the colon can be established. Suggestions for possible future investigation are provided.
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PMID:Role of dietary fiber in diverticular disease and colon cancer. 626 84

Epidemiological data have provided clues to the etiological factors involved in large bowel cancer development. High intake of dietary fat tends to promote colon carcinogenesis. Studies in metabolic epidemiology have shown that the high dietary fat affects the metabolic activity of gut bacteria as well as the levels of secondary bile acids that may act as tumor promoters for the colon. Animal model studies indicate that total dietary fat, rather than type of fat, exerts a promoting role in colon carcinogenesis.
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PMID:Dietary fat and its relationship to large bowel cancer. 626 60

Analysis of the etiologic factors and relevant mechanisms involved in carcinogenesis leads to a classification of agents involved in the carcinogenic process as genotoxic or epigenetic. Their mode of action is distinct, especially with regard to dose-response effects and reversibility. The genotoxic carcinogens for colon cancer are unknown, but mutagenic components found in fried beef and fish are under study. Epigenetic agents as promoting factors play a major role in the development of cancer of the colon. Specific nutritional elements associated with colon cancer risk are high fat diets, high cholesterol intake, and low fiber intake. The role of micronutrients as modulators and inhibitors needs to be explored. Through metabolic studies in diverse populations and in reliable animal models, it is now clear that dietary fat and cholesterol control the total flow of bile acids in lumen and a high-fat, high-cholesterol diet increases the total of bile acids in the gut. Bile acids but not neutral sterols have promoting effects and are related to colon cancer risk although bile acids by themselves do not act as complete carcinogens. The effect of dietary fiber such as cereal bran is to increase stool bulk which dilutes the concentration of bile acids. Reducing the concentration of bile acids either by lower dietary fat and cholesterol or by increasing dietary fiber may effectively lower the risk for colon cancer.
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PMID:Bile acids, but not neutral sterols, are tumor promoters in the colon in man and in rodents. 630 78


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