Differential mechanisms of increased alpha 1-fetoprotein production in rats following carbon tetrachloride injury and partial hepatectomy.

Possible differences in the mechanisms of increased alpha1-fetoprotein (AFP) production following carbon tetrachloride (CCl4) intoxication and partial hepatectomy were studied with 5-week-old rats at the time of sacrifice. The maximum level of serum AFP reached in 4 days after a single dose of CCl4 was much higher than that after partial hepatectomy, although the incorporation of [3H]thymidine into liver DNA increased nearly to the same extent by either of these treatments. In the remnant after partial hepatectomy, the DNA synthesis that was further accelerated by treatment with a lower dose of thioacetamide was not associated with any further increases of serum AFP levels. However, CCl4 given to partially hepatectomized rats had an additive effect on increased AFP levels. The increases of serum AFP concentrations in CCl4-injured rats had an additive effect on increased AFP levels. The increases of serum AFP concentrations in CCl4-injured rats were depressed by Mitomycin C given in vivo, whereas the increases in partially hepatectomized rats were not. Treatment with 8-azaguanine inhibited both increase of serum AFP levels, although the inhibition was much less or was insignificant in partially hepatectomized rats. These results suggest that existence of different underlying mechanisms of the increased AFP production for the two experimental conditions.