Alpha-fetoprotein in the woodchuck model of hepadnavirus infection and disease: immunochemical analysis of woodchuck alpha-fetoprotein and measurement in serum by quantitative monoclonal radioimmunoassay.
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 alpha-fetoprotein and woodchuck hepatitis virus-induced hepatocellular carcinoma in the woodchuck model, we produced a monoclonal antibody to woodchuck alpha-fetoprotein and used biophysical and immunochemical methods to demonstrate its specificity and affinity (7 x 10(8) L/mol) for woodchuck alpha-fetoprotein. A competition radioimmunoassay was then developed and standardized for measuring serum alpha-fetoprotein concentrations. In the radioimmunoassay system, woodchuck alpha-fetoprotein was detected between 20 ng/ml (20% to 25% inhibition) and 8,500 ng/ml (97% to 98% inhibition). Elevated serum alpha-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 alpha-fetoprotein was elevated above normal (greater than or equal to 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 alpha-fetoprotein became markedly elevated above normal in woodchuck hepatitis virus-carrier woodchucks that developed hepatocellular carcinoma but not in serologically recovered or uninfected woodchucks (i.e., without hepatocellular carcinoma). Thus, alpha-fetoprotein may provide a useful noninvasive marker in the woodchuck model for detecting and monitoring woodchuck hepatitis virus-induced hepatocellular carcinoma from earlier stages.
Department of Microbiology, Georgetown University Medical Center, Rockville, Maryland 20852.
P J
PJ
Cote
C
C
Pohl
J
J
Boyd
B C
BC
Tennant
J L
JL
Gerin
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000915:Antibody Affinity; D000918:Antibody Specificity; D015613:Hepadnaviridae; D007120:Immunochemistry; D008392:Marmota; D011863:Radioimmunoassay / Q000379:methods*; D012015:Reference Standards; D014777:Virus Diseases / Q000097:blood / Q000378:metabolism*; D000509:alpha-Fetoproteins / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000509:alpha-Fetoproteins