Autoradiographic analysis of hepatocytes in mirex-induced adaptive liver growth

The relationships between [3H]thymidine incorporation into hepatocyte nuclei, cell enlargement, and mitotic index were studied in intact (INT) and adrenalectomized (ADX) mirex-dosed rats. In INT mirex-dosed rats the sequence of events included the following: a biphasic response in nuclear labeling of mononuclear hepatocytes with peaks at 48 and 66 h postmirex dose, a peak in mitotic activity 66 h postmirex dose, and a significant increase in binuclear hepatocyte size 48 h postmirex dose. In ADX mirex-dosed rats the sequence of events included the following: a biphasic response in nuclear labeling of mononuclear hepatocytes with peaks at 24 and 48 h postmirex dose, a peak in mitotic activity 60 h postmirex dose, and a marginal increase in binuclear hepatocyte size 48 h postmirex dose. Corticosterone supplements to ADX mirex-dosed rats significantly reduced nuclear labeling of the mononuclear hepatocytes and increased the size of binuclear hepatocytes to that observed in INT mirex-dosed rats. This study demonstrates that adaptive liver growth consists of a hyperplastic response that involves mononuclear hepatocytes and a hypertrophic response that involves binuclear hepatocytes. Both responses appear to be modulated by corticosterone.