Reversibility and irreversibility of liver tumors in mice induced by the alpha isomer of 1,2,3,4,5,6-hexachlorocyclohexane

Abstract

The characteristics of liver tumors in mice induced by the alpha isomer of 1,2,3,4,5,6-hexachlorocyclohexane (alpha-BHC), were studied with emphasis on their reversibility of irreversibility. Male 8-week-old DDY mice were fed basal diet supplemented with 500 ppm of alpha-BHC for 16, 20, 24, and 36 weeks and then were fed basal diet without alpha-BHC for 4, 8, 12, 16, 24, or 36 weeks. At various intervals, 13 to 20 mice were killed for light and electron microscopic observations. The incidences of liver tumors in mice induced by alpha-BHC increased progressively on continuous administration of alpha-BHC, but when its administration was discontinued some tumors disappeared. Histologically, after alpha-BHC administration for 24 weeks, most tumors were nodular hyperplasias, and there were only a few well-differentiated hepatocellular carcinomas. However, 60 or 72 weeks after the beginning of the experiment, most of the liver tumors were hepatocellular carcinomas and there were only a few nodular hyperplasias. At a later stage, 60 or 72 weeks, the liver parenchymal tissue in nontumorous areas was essentially normal, but small foci were occasionally seen in nontumorous areas that were composed of remaining hyperplastic nodular cells, phagocytic cells, Kupffer cells, and leukocytes. These findings suggest that the reversible tumors were usually nodular hyperplasias whereas the irreversible tumors were hepatocellular carcinomas. After alpha-BHC administration was stopped, many mesenchymal cells infiltrated the nodular hyperplastic lesions, and degenerated liver cells were found. These observations indicate that mesenchymal cell elements may be important in reversing the growth of liver tumors induced by alpha-BHC.