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
Earlier investigations by Miller and Miller') have clearly demonstrated that the N-hydroxylated metabolite of N-2-fluorenylacetamide is the proximate carcinogen, but there is no definite evidence that metabolites of the polynuclear hydrocarbons fit into this category. Many polycyclic aromatic hydrocarbons are metabolized by oxydation of the more reactive bonds of the ring system : in contrast, the methyl groups of this derivative are the most reactive molecular sites. The main products of oxidation of 7,12-DimethylbenzCa)anthracene (DMBA) by liver homogenates are the isomeric monohydroxyl derivatives. 2) Sufficient experimental data have been accummulated to establish the fact that 7-Hydroxymethyl-12-methylbenzCajanthracene (7-OHMe-12-Me-BA), a metabolite of DMBA, is a more powerful adrenocorticolytic agents than the parent compoud. 3) 4) 5) 8) 7) 8) Both DMBA and 7-OHMe-12-Me-BA induce cancer in rats 3) 5) 9) 10) and mice , 3) 11) but 7-OHMe-12-Me-BA appears to be a less effective carcingen. Lipid emulsions containing polynuclear hydrocarbons could be prepared and injected intravenously into animals. 7) 12) Injection of a pulse dose of a concentrated emulsion of a hydrocarbon is a simple and useful method of introducing a considerable amout of a compound into the blood. It has been recently more distinct in the observations on a pulse dose of both agents that the adrenocorticolytic effect of 7-OHMe-12-Me-BA is stronger than that of DMBA. 7) To examine the biologic action of a pulse dose of both compounds into the rodents, changes in body weight, damage to hemopoietic and adrenocortical tissues, and carcinogenecity in some tissues were the criteria used for evaluation of biologic activities. The experimental results are presented in this communication. Materials and Methods Lipid Emulsions of Polynuclear Hydrocarbons Both DMBA, m. p. 122-'123 °C, and 7-OHMe-12-Me-BA , m. p.
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