Uptake and Clearance of 7, 12-Dimethylbenz [a] anthracene Injected Intravenously to Rats on High Fat Diets

Abstract

There is considerable evidence to support that the unique sensitivity of certain tissues to systemic administration of carcinogenic agents is due, in part, to localization of the agents within them. In general, hydrocarbons are cleared from the body rapidly.1) In contrast, the adipose tissues are slow in clearing carcinogens. 2) 3) In the mammary adipose tissue, the fat pad might appear to act as a carcinogen trap, retaining the unchanged hydrocarbon within the fat cells, from which it is released slowly. Mammary carcinogenesis with 7,12-dimethylbenz Cap anthracene (DMBA) was enhanced by the high fat diets given to the host, especially a high corn oil diet. 4) 5) The influence might be due either to an abnormal trap of the altered adipose tissue or to direct and indirect effects of the ingested upon the metabolism of tumor tissues. To examine how a high fat diet acts mammary carcingenesis, an experiment was carried out in which the concentration of labeled DMBA in various organs of the rats on high fat diets was determined at various time intervals after a single intravenous injection of hot DMBA emulsion.The results of the investigation are presented in this communication. Materials and MethodsBy means of our procedure, 8) 2.5 or 5 mCi of 9, 10-Dimethy1-1, 2-benzanthracene-T (G), The Radiochemical Centre, Amersham, was incorporated to 20 ml of DMBA emulsion made by Upjohn Co., U.S.A.. When 5 mCi of the compound was incorporated, 1 ml of the emulsion prepared contains 4.96 mg of DMBA, the ratio of hot DMBA per cold one in which is 1/700, and exhibits 250pCi.Twenty four Sprague-Dawley female rats. aged 55 days and weighed approximately 170g, of the control diet group were injected by 1 ml of the radioactive emulsion containing 0.25 mCi from a caudal vein. The concentrations of labeled DMBA in serum , liver, kidney, adrenal gland, and abdominal mammary fatty pad were determined at 10 , 30, and 180 minutes, and 0.5, 1, 3, 5, and 7 days after the administration. Three rats were sacrificed by decapitation for each stage. The definite amount , weighed on a torsion balance, of the tissue determined was homogenized in hexane-ethanol mixture