Cote P J, Pohl C, Boyd J, Tennant B C, Gerin J L
Department of Microbiology, Georgetown University Medical Center, Rockville, Maryland 20852.
Hepatology. 1990 May;11(5):824-33. doi: 10.1002/hep.1840110518.
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.
东部土拨鼠感染土拨鼠肝炎病毒是研究人类乙型肝炎病毒感染及相关疾病（包括肝细胞癌）的有用模型。在人类中，肝细胞癌常通过检测血清甲胎蛋白进行监测。为了在土拨鼠模型中研究甲胎蛋白与土拨鼠肝炎病毒诱导的肝细胞癌之间的关系，我们制备了抗土拨鼠甲胎蛋白的单克隆抗体，并采用生物物理和免疫化学方法证明其对土拨鼠甲胎蛋白的特异性和亲和力（7×10⁸ L/mol）。随后建立并标准化了一种竞争放射免疫测定法，用于测量血清甲胎蛋白浓度。在该放射免疫测定系统中，可检测到浓度在20 ng/ml（抑制率20%至25%）至8500 ng/ml（抑制率97%至98%）之间的土拨鼠甲胎蛋白。在23只处于土拨鼠肝炎病毒诱导的肝细胞癌晚期的土拨鼠中，有21只的血清甲胎蛋白浓度升高（450至452000 ng/ml）。在16只携带土拨鼠肝炎病毒的土拨鼠中，有11只在终末期肝细胞癌出现前3至11个月，血清甲胎蛋白就已升高至正常水平以上（≥450 ng/ml）。在一项初步研究中，携带土拨鼠肝炎病毒且发生肝细胞癌的土拨鼠血清甲胎蛋白显著高于正常水平，但血清学恢复或未感染的土拨鼠（即未发生肝细胞癌）则没有这种情况。因此，在土拨鼠模型中，甲胎蛋白可能是一种有用的非侵入性标志物，可用于从早期阶段检测和监测土拨鼠肝炎病毒诱导的肝细胞癌。
