Hepatoma-Associated Alterations of Serum α1-Antitrypsin in LEC Rats

Abstract

LEC rats have been established as a new mutant strain which develops hereditary hepatitis [1–3] and spontaneous hepatocellular carcinomas (hepatomas) [4]. However, the mechanisms of the development of the sequential diseases in LEC rats are not yet known precisely. Hepatic cirrhosis in human infancy or early childhood is known to be associated with alpha₁-antitrypsin (α₁AT) deficiency [5]. In adults, α₁ AT deficiency was described in association with cirrhosis and portal fibrosis of the liver [6–8]. Furthermore, α₁AT deficiency showed a high risk for cirrhosis and primary liver cancer [9]. This deficiency indicates an autosomal recessive mode of inheritance [5, 9]. Experimental rat α₁AT deficiency produced by galactosamine-treatment was characterized previously [10, 11]. However, the relation between rat α₁AT and liver disease has not been reported, although rat α₁AT is known to be a glycoprotein which acts as a liver protease inhibitor in plasma and to have several forms produced by sialylation in parental molecules [12–14]. Therefore, our interest was focused on the α₁AT of LEC rats which develop hereditary hapatitis and liver cancer. In this study, characteristics of serum α₁AT in LEC rats are described.