QUANTITATIVE-EVALUATION OF THE PROMOTION BY 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN OF HEPATOCARCINOGENESIS FROM DIETHYLNITROSAMINE

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (10) , 3616-3620
Abstract
In order to test the potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a promoter of hepatocarcinogenesis, rats which had received a single 10 mg/kg dose of diethylnitrosamine (DEN) following partial hepatectomy were given TCDD (0.14 and 1.4 .mu.g/kg s.c. once every 2 wk) for 7 mo. Animals which received only a single initiating dose of DEN after partial hepatectomy and no further treatment or TCDD alone with no initiating dose of DEN exhibited relatively few enzyme-altered foci and no hepatocellular carcinomas. However, animals initiated with DEN and then given TCDD had a marked increase in enzyme-altered foci. At the higher dose of TCDD, hepatocellular carcinomas were present in 5 of 7 rats. By means of 3 different enzyme markers used to evaluate the phenotypes of the enzyme-altered foci, a distinct phenotype heterogeneity of the foci was noted with a shift towards phenotypes exhibiting a greater deviation from normal liver when TCDD was given following DEN-partial hepatectomy. The number of enzyme-altered foci was quantified by relating measurements made from 2-dimensional tissue sections to the numbers of foci per unit volume of liver using relationships established in the field of stereology. The total volume of the liver occupied by the enzyme-altered foci, but not their number, increased with the dose of TCDD administered following DEN-partial hepatectomy. TCDD is a potent promoting agent for hepatocarcinogenesis.