INCREASED ALPHA-1-FETOPROTEIN PRODUCTION IN RAT-LIVER INJURIES INDUCED BY VARIOUS HEPATOTOXINS

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 67  (2) , 279-287
Abstract
The development of a highly sensitive method of AFP quantitation by a competitive binding radioimmunoassay has enabled detection of the increase in serum AFP level in patients with viral hepatitis and liver cirrhosis without proved malignancy. Serum .alpha.1-fetoprotein (AFP) concentration in 5 wk 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 CCl4, 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 glucoso-6-phosphate dehydrogenase (G-6-PD) among biochemical parameters studied for hepatocellular injuries. The difference in time courses of the increase in liver G-6-PD activity and serum AFP level following CCl4 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 CCl4-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 CCl4. Treatment with a lower dose of thioacetamide resulted in little 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. Administration of ethionine, which caused little necrosis of liver cells, produced increased serum AFP and liver G-6-PD levels with only a small increase of hepatic DNA synthesis compared to those following thioacetamide as well as CCl4. 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.