Effects of Cholestyramine on 1,2-Dimethylhydrazine-Induced Enteric Carcinoma in Germfree Rats

Asano, Tomoaki; Pollard, Morris; Madsen, David C.

doi:10.3181/00379727-150-39124

Cited by 40 publications

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“…Studies by other investigators showed that dietary CHST Discussion promotes cancers of colon (Nigro et al, 1973;Asano et al, 1975) and pancreas (Brand & Morgan, 1982). In these The end point of this study is the size and the incidence of studies bile acids were implicated as the cause of the tumour malignant tumours (Figure 1; Table II) after 200 days of diet promotion.…”

Section: Srmlpdaayementioning

confidence: 99%

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Cholestyramine promotes 7,12-dimethylbenzanthracene induced mammary cancer in Wistar rats

Melhem¹,

Gabriel²,

Eskander³

et al. 1987

Br J Cancer

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Summary The promotion of 7,12-dimethylbenzanthracene (DMBA) induced mammary cancer in Wistar rats by a 4% cholestyramine (CHST) diet was investigated. The rats, 50 days of age, were divided into six groups. First two groups were given an intragastric dose of 0.8 ml of corn oil whereas the remaining four groups were given a single intragastric dose of 5 mg of DMBA dissolved in 0.8 ml of corn oil. After 1 week on laboratory chow the first two groups and two groups treated with DMBA were fed a control diet and the two remaining groups treated with DMBA were fed a 4% CHST diet. Half the animals were killed at 100 days and the remainder at 200 days. A detailed histologic examination of grossly normal mammary tissue as well as any tumour mass was made for each rat. The serum lipids were extracted and the individual neutral lipid composition was determined. In rats treated with DMBA and fed a 4% CHST diet, the incidence of malignant tumours increased by 5 fold, and the tumour weight by 12 fold. In addition, the serum total lipids, cholesterol esters and triglycerides decreased significantly when compared with rats fed a control diet. These results suggest that CHST diet promotes DMBA cholesterol levels by 12%, resulting in a 19% reduction in At 50 days of age, they were divided into 6 groups and deaths due to coronary heart disease (CHD). Based on these subjected to the following treatments: 4 animals each in studies it has been widely accepted that a reduction in the groups a and b were given a single intragastric dose of 0.8ml serum cholesterol levels will significantly reduce the risk of corn oil alone by a stomach tube; 5 animals in group c, 7 CHD in humans (Rifkind, 1986). While this conclusion may animals in group d, 6 animals in group e, and 10 animals in be warranted, some epidemiological studies have shown that group f were each given 5 mg of DMBA dissolved in 0.8 ml a reduction in serum cholesterol levels resulted in increased of corn oil. All the animals were fed laboratory chow (Allied incidence of all cancers and colon cancer in particular Mills Inc., Chicago, IL) for the next 7 days, then switched to (Graham 1984). Some scientists concluded that treatment semipurified diets (ICN Pharmaceuticals Inc. Cleveland, with cholestyramine increases the risk for cancer (Vitale & OH). The control semipurified diet (AIN) was prepared as Ross, 1985). If indeed CHST or low serum cholesterol levels recommended by the American Institute of Nutrition (Bieri increase the risk for cancer, the mechanism by which this is et al., 1977). This diet contained 50g sucrose, 20g casein, brought about is unknown. There are only three published 15g corn starch, 0.3g methionine, 5g cellulose, 5g corn oil, reportsa which showed conclusively that CHST promotes 1 g vitamin mixture, 3.5 g mineral mixture and 0.2 g choline. cancers in rats. Nigro et al (1973) showed that at 2% level A 4% CHST diet was prepared by substituting 4 g of pure in the dietn CHST promotes colon cancer in male Sprague-cholestyramine resin (Bristol-Meyers Company,...

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Section: Srmlpdaayementioning

confidence: 99%

“…All the promotes DMH induced colon cancers in germ free rats animals had free access to food and water. Groups a, c and e (Asano et al, 1975). Recently it was reported that CHST at were sacrificed at the end of 100 days and groups b, d and f 2, 6 and 10% level in the diet stimulates pancreatic growth, were sacrificed at the end of .200 days.…”

mentioning

confidence: 99%

Cholestyramine promotes 7,12-dimethylbenzanthracene induced mammary cancer in Wistar rats

Melhem¹,

Gabriel²,

Eskander³

et al. 1987

Br J Cancer

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“…Much experimental evidence for the promotional effect of bile acids, binding agents, or fatty acids has generally been sought by exposing rodents to such agents while concurrently treating the animals with one of a variety of chemical colon carcinogens [7][8][9][15][16][17][18]. In most of these studies, the promoters for colorectal carcinogenesis were thought to be secondary BAs such as LCA and DCA [7,8,15,17,18].…”

Section: Discussionmentioning

confidence: 99%

“…In most of these studies, the promoters for colorectal carcinogenesis were thought to be secondary BAs such as LCA and DCA [7,8,15,17,18]. However, primary BAs such as CA and CDCA have been reported to act as colon tumor promoters in experimental studies using germ-free rats [9,16]. In the present experiment, colorectal tumors were induced by a combination of azoxymethane pretreatment and DSSinduced colitis in group A, whereas no colorectal tumor was induced by saline pretreatment and DSS administration in group C. This result suggests that DSS-induced colitis acts as a promoter for colorectal carcinogenesis by azoxymethane [3].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Fecal Bile Acids and the Occurrence of Colorectal Neoplasia in Experimental Murine Ulcerative Colitis

Kajiura

Ohkusa²,

Okayasu³

1998

Digestion

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Objective: The possible role of fecal bile acids in colorectal carcinogenesis in ulcerative colitis has been reported. In this study, we investigated the relationship between fecal bile acids and the occurrence of colorectal neoplasia in experimental murine colitis induced by dextran sulfate sodium. Methods: Colorectal neoplasia in experimental colitis was induced by dextran sulfate sodium subsequent to a single azoxymethane pretreatment. Fecal bile acids were analyzed by gas-liquid chromatography. Results: Multiple high-grade dysplasias (intramucosal adenocarcinoma) and inflammatory changes were seen in all mice administered dextran sulfate sodium and azoxymethane. Inflammatory changes were also observed in all mice given dextran sulfate sodium only, while neither tumor nor inflammatory changes were detected in any of the control mice. Significant increases in cholic acid were observed in the mice of the colorectal tumor and experimental colitis groups during the experimental period, while in the control mice, no significant changes in fecal bile acids were obseved. Conclusion: It is suggested that fecal cholic acid and colitis may be intimately related to the development of colorectal neoplasia in this experimental model of murine colitis as well as in ulcerative colitis.

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“…One such agent, cholestyramine, has already been implicated in the development of colon cancer in man [20] and has been claimed to promote colon cancer induced in rats by dimethylhydrazine [2,16]. Aluminium hydroxide (Aludrox), a widely used antacid, also binds bile salts, both in vitro [6] and in vivo [22], and this property is used therapeutically in man to counteract bile salt-mediated diarrhoea [22].…”

Section: Introductionmentioning

confidence: 99%

Experimental Evidence against the Bile Salt Theory of Colon Carcinogenesis

Cruse¹,

Lewin²,

Ferulano³

et al. 1981

Eur Surg Res

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According to the bile salt theory of colon carcinogenesis, therapeutic agents which increase the delivery of bile salts to the large intestine may promote colon cancer. The possibility that aluminium hydroxide (Aludrox), a bile salt binding agent, might facilitate colon carcinogenesis in vivo was tested experimentally, using the dimethylhydrazine (DMH)-induced rat colon cancer model. 48 Wistar rats were randomly allocated to 1 of 3 groups, all fed the same standard diet. Two groups received a course of ten weekly DMH injections. One was allowed fresh drinking water ad libitum whilst the other received Aludrox in their drinking water. A third group received weekly saline injections plus Aludrox in their drinking water. After 1 year’s observation, there were no significant differences between the groups of DMH-injected rats given drinking water with or without Aludrox in respect of survival, necropsy incidence of primary or metastatic colon cancer, or in the total number of colon tumours per group. The results provide reassurance that Aludrox does not promote colon cancer and tend to contradict the bile salt theory of colon carcinogenesis.

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Effects of Cholestyramine on 1,2-Dimethylhydrazine-Induced Enteric Carcinoma in Germfree Rats

Cited by 40 publications

References 0 publications

Cholestyramine promotes 7,12-dimethylbenzanthracene induced mammary cancer in Wistar rats

Cholestyramine promotes 7,12-dimethylbenzanthracene induced mammary cancer in Wistar rats

Relationship between Fecal Bile Acids and the Occurrence of Colorectal Neoplasia in Experimental Murine Ulcerative Colitis

Experimental Evidence against the Bile Salt Theory of Colon Carcinogenesis

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