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

Abstract

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,...

Elevated K-ras activity with cholestyramine and lovastatin, but not konjac mannan or niacin in lung—–Importance of mouse strain

“…Normal mouse lung tissue was used in our study, thus K-ras would be expected to act as a tumor suppressor in this context [4][5][6]21]. However, published studies in colon and mammary gland show CS to be a tumor promoter [22,23]. This may seem at odds with the conception of wild-type K-ras as a tumor suppressor in normal lung.…”

Statins and Cancer Development

“…This result suggests that the induction of mevalonate synthesis in extrahepatic tissues that follows statin-mediated serum cholesterol reduction may promote the growth of occult neoplastic or preneoplastic cells (7). Indeed, in rodents, lowering of serum cholesterol by the unabsorbed bile acid -binding resin cholestyramine has been shown to promote mammary gland carcinogenesis (8,9). There is evidence, however, that diffusion-mediated uptake of the lipophilic statins mitigates the increase in mevalonate synthesis in extrahepatic tissues that accompanies the decrease in serum cholesterol that they induce (10).…”

Chemoprevention of DMBA-Induced Mammary Tumors in Rats by a Combined Regimen of Alpha-Tocopherol, Selenium, and Ascorbic Acid

“…Several agents have been characterized as effective in cancer chemoprevention, but studies are not yet conclusive (3). Chemoprevention properties of vitamins and other micronutrients as single agents or complex mixtures (4–22), fatty acids and related substances (23–27), monoterpens (28), hormones, and related chemical agents (1–3,29) have been studied in experimental models. To assess the efficacy of potential chemopreventive agents it is important to develop sensitive and selective methods for determining molecular, metabolic, and cellular transformations that are relevant to the process of carcinogenesis in mammary tissue.…”