Reversibility and Irreversibility of Liver Tumors in Mice Induced by the e Isomer of 1,2,3,4,5,6- Hexachlorocyclohexane

The characterist ics of liver tumors in mice induced by the o~ isomer of 1,2,3,4,5,6-hexachlorocyclohexane (~x-BHC), were studied with emphasis on their reversibil i ty or irreversibility. Male 8-week-old DDY mice were fed basal diet supplemented w i th 500 ppm of e-BHC for 16, 20, 24, and 36 weeks and then were fed basal diet wi thout (x-BHC for 4, 8, 12, 16, 24, or 36 weeks. At various intervals, 13 to 20 mice were killed fo r l ight and electron microscopic observations. The incidences of liver tumors in mice induced by o~-BHC increased progressively on cont inuous administrat ion of o~BHC, but when its administrat ion was discont inued some tumors disappeared. Histologically, after (x-BHC administration for 24 weeks, most tumors were nodular hyperplasias, and there were only a few well-dif ferentiated hepatocellular carcinomas. However, 60 or 72 weeks after the beginning of the experiment, most of the liver tumors were hepatocel lular carcinomas and there were only a few nodular hyperplasias. At a later stage, 60 or 72 weeks, the liver parenchymal t issue in nontumorous areas was essentially normal, but smal l foci were occasional ly seen in nontumorous areas that were composed of remaining hyperplastic nodular cells, phagocytic cells, Kupffer cells, and leukocytes. These f indings suggest that the reversible tumors were usuarly nodular hyperptasias whereas the irreversible tumors were hepatocel lular carcinomas. After o~-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 l iver tumors induced by e-BHC.