ABSTRACT
Female Wistar rats were given 5 mg of 7,12-dimethylbenz[a]anthracene (DMBA) and fed either a control diet (AIN), a 4% cholestyramine (CHST) diet, a 2% corn oil plus 18% coconut oil (saturated fat) diet, a 20% corn oil [unsaturated fatty acid (USF)] diet, or a USF + 4% cholestyramine (USF + CHST) diet. The mammary glands, tumors, livers, and sera were analyzed for lipids, de novo cholesterogenesis, and serum lecithin-cholesterol acyltransferase (LCAT) activity levels. Level and type of fat in the diet, DMBA, CHST, and length of feeding influenced the lipid composition of liver and mammary tissues. Stimulation of de novo cholesterogenesis in the mammary gland and depression in circulating LCAT activity levels correlated with the incidence and growth of mammary tumors, suggesting that stimulation of de novo cholesterogenesis plays an important role in mammary cancer development.
Subject(s)
Cholesterol/biosynthesis , Lipids/analysis , Mammary Glands, Animal/metabolism , Mammary Neoplasms, Experimental/metabolism , Animals , Cholestyramine Resin/administration & dosage , DNA/biosynthesis , Fatty Acids, Unsaturated/administration & dosage , Female , Rats , Rats, Inbred Strains , Receptors, LDL/analysisABSTRACT
Promotion of 7,12-dimethylbenzantracene (DMBA)-induced mammary cancer in Wistar rats, by diets containing unsaturated fat (USF) and unsaturated fat plus 4% cholestyramine (USF+ CHST) was compared to that in rats fed saturated fat (SF). The diets were fed for 100 or 200 days. Histologic examination of grossly normal mammary tissue, as well as of any tumor mass, showed a significant increase in the incidence and size of mammary tumors in USF and USF + CHST groups when compared to SF group. Moreover, in the USF + CHST group one tumor developed in one rat as early as 100 days. The serum total lipids, triglycerides and cholesterol esters decreased significantly at 200 days in USF and USF + CHST groups. These results suggest that a diet high in unsaturated fat alone, or in combination with 4% cholestyramine, promotes DMBA-induced mammary cancer in Wistar rats.
Subject(s)
Cholestyramine Resin/pharmacology , Dietary Fats/pharmacology , Fatty Acids, Unsaturated/pharmacology , Mammary Neoplasms, Experimental/pathology , 9,10-Dimethyl-1,2-benzanthracene , Animals , Drug Synergism , Female , Mammary Neoplasms, Experimental/chemically induced , Rats , Rats, Inbred StrainsABSTRACT
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 induced mammary cancers in Wistar rats.
