Effect of phenobarbital on the altered biochemical phenotypes expressed by hyperplastic liver nodules during hepatocarcinogenesis in the rat.

The effects of a chronic 8- to 12-week administration of the hepatic tumor promoter, phenobarbital, on further altering the biochemical enzyme deviation patterns shown by hyperplastic liver nodules was examined in rats previously subjected to the initiation/selection protocol of Solt and Farber. Hyperplastic liver nodules of various size classes from the phenobarbital-treated group exhibited a significant increase in GGT specific activity, as well as 2- to 3-fold higher levels of microsomal cytochrome P-450 than was shown by control nodules. The increase in GGT specific activity was also found in many cases to be higher in those hyperplastic liver nodules from the phenobarbital-treated group with diameters greater than 3.0-3.5 mm than in nodules of a smaller size. In contrast, the GGT specific activity of the control nodules did not correlate with differences in their sizes. Furthermore, while histochemical staining of GGT activity appeared uniform in sections of the various sized hyperplastic nodules from the phenobarbital-treated group, biochemical measurements indicated a consistently higher specific activity for this enzyme in tissue taken from the central portion of the nodule than in tissue from the peripheral portion of the nodule. On the other hand, the specific activities of glucose-6-phosphatase, 5'-nucleotidase, and fructose-1,6-diphosphate aldolase of the hyperplastic liver nodules were not found to be significantly altered over control values by the chronic phenobarbital treatment, suggesting a stability of these other marker enzyme alterations during the early promotional phase of hepatocarcinogenesis.