α–Fetoprotein in the Woodchuck Model of Hepadnavirus Infection and Disease: Immunochemical Analysis of Woodchuck α–Fetoprotein and Measurement in Serum by Quantitative Monoclonal Radioimmunoassay

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Abstract
Woodchuck hepatitis virus infection of the eastern woodchuck represents a useful model for the study of hepatitis B virus infection and disease in humans, including hepatocellular carcinoma. In man, hepatocellular carcinoma is frequently detected and monitored using assays for serum alpha–fetoprotein. To study the relationship between α–fetoprotein and woodchuck hepatitis virus–induced hepatocellular carcinoma in the woodchuck model, we produced a monoclonal antibody to woodchuck α–fetoprotein and used biophysical and immunochemical methods to demonstrate its specificity and affinity (7 × 108 L/mol) for woodchuck α–fetoprotein. A competition radioimmunoassay was then developed and standardized for measuring serum α–fetoprotein concentrations. In the radioimmunoassay system, woodchuck α–fetoprotein was detected between 20 ng/ml (20% to 25% inhibition) and 8,500 ng/ml (97% to 98% inhibition). Elevated serum α–fetoprotein concentrations (450 to 452,000 ng/ml) were measured in 21 of 23 woodchucks in the advanced stages of woodchuck hepatitis virus–induced hepatocellular carcinoma. Serum α–fetoprotein was elevated above normal ( ≥ 450 ng/ml) as early as 3 to 11 mo before terminal hepatocellular carcinoma in 11 of 16 of the woodchuck hepatitis virus–carrier woodchucks. In a pilot study, serum α–fetoprotein became markedly elevated above normal in woodchuck hepatitis virus–carrier woodchucks that developed hepatocellular carcinoma but not in serologically recovered or uninifected woodchucks (i. e., without hepatocellular carcinoma). Thus, α–fetoprotein may provide a useful nonivasive marker in the woodchuck model for detecting and monitoring woodchuck hepatitis virus–induced hepatocellular carcinoma from earlier stages.(HEPATOLOGY 1990; 11:824–833.)