title: Increased alpha1-fetoprotein production in rat liver injuries induced by various hepatotoxins.
abstract: Serum alpha1-fetoprotein (AFP) concentration in 5-week-old rats was measured by the radioimmunoassay technique after a single administration of various hepatotoxins. Marked elevation of serum AFP concentrations occurred in rats treated with carbon tetrachloride, thioacetamide, D-galactosamine, allyl alcohol, allyl formate, and ethionine in 4 days of these treatments. The increased production of AFP appeared to be correlated with the induction of liver glucose-6-phosphate dehydrogenase (G-6-PD) among biochemical parameters studied for hepatocellular injuries. However, the difference in time courses of the increase in liver G-6-PD activity and serum AFP level following CC14 treatment suggested that the increased production of serum AFP and the induction of G-6-PD in injured liver were caused by closely related but different mechanisms. Pretreatment of CC14-injured rats with N,N'-diphenyl-p-phenylenediamine or aminoacetonitrile was effective not only in lowering the increased level of serum AFP and liver G-6-PD but also in preventing liver cell necrosis and steatosis induced by CC14. Treatment with a lower dose of thioacetamide resulted in littel elevation of serum AFP and liver G-6-PD with a markedly increased incorporation of 3H-thymidine into liver DNA without any evidence of liver injury. On the other hand, the administration of ethionine, which caused little necrosis of liver cells, produced increase in both serum AFP and liver G-6-PD levels with an only small increase of hepatic DNA synthesis compared to those following thioacetamide as well as CC14. These results suggest that the elevation of serum AFP is not directly related to the stimulation of hepatic DNA synthesis. Some additional mechanisms of specific gene amplification for AFP, which is geared to hepatic injury per se, appear to play a major role in the increased AFP production in injured liver.
mesh_terms: D000607:Aminoacetonitrile / Q000494:pharmacology; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury; D004247:DNA / Q000096:biosynthesis; D005001:Ethionine / Q000494:pharmacology; D005326:Fetal Proteins / Q000096:biosynthesis*; D005954:Glucosephosphate Dehydrogenase / Q000096:biosynthesis; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D013853:Thioacetamide / Q000494:pharmacology; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
chemical_list: D005326:Fetal Proteins; D000509:alpha-Fetoproteins; D013853:Thioacetamide; D000607:Aminoacetonitrile; D004247:DNA; D002251:Carbon Tetrachloride; D005954:Glucosephosphate Dehydrogenase; D005001:Ethionine