Schmidt W N, Page D L, McKusick K, Hnilica L S
Carcinogenesis. 1985 Aug;6(8):1147-53. doi: 10.1093/carcin/6.8.1147.
Monoclonal or affinity-purified antibodies specific to Novikoff hepatoma cytokeratin p39 were employed to study the origin and fate of p39-containing cell types during hepatocarcinogenesis induced with N,N-dimethyl-p(m-tolylazo)aniline. Frozen sections were obtained from the livers of animals autopsied temporally during carcinogen feeding and were assayed immunohistochemically. In normal, untreated liver or in liver from animals fed the hepatotoxin alpha-naphthyl-isothiocyanate, the localization of p39 was restricted to bile duct epithelial cells while hepatocytes were non-reactive. However, during carcinogen treatment we observed a sequential appearance of immunoreactive cells which were similar morphologically to the classical 'oval' cells of hepatocarcinogenesis; eventually these cell types were enriched around the preneoplastic hepatocyte nodules. Occasional transformed hepatocytes within the nodules exhibited strong immunoreactivity. In the later stages of hepatocarcinogenesis, these antibodies stained the epithelial cells in areas of severe adenosis as well as the neoplastic epithelial cells of cholangiomas and some, but not all, hepatocellular carcinomas. Our results document the presence of p39 in the 'oval' cells of hepatocarcinogenesis and indicate that some populations of transformed hepatocytes exhibit this cytokeratin after transformation.
使用对诺维科夫肝癌细胞角蛋白p39具有特异性的单克隆抗体或亲和纯化抗体，来研究在用N，N-二甲基-p（间甲苯基偶氮）苯胺诱导肝癌发生过程中含p39细胞类型的起源和命运。在致癌物喂养期间，从经尸检的动物肝脏获取冰冻切片，并进行免疫组织化学检测。在正常的未处理肝脏或喂食肝毒素α-萘基异硫氰酸盐的动物肝脏中，p39的定位仅限于胆管上皮细胞，而肝细胞无反应。然而，在致癌物处理过程中，我们观察到免疫反应性细胞依次出现，其形态与肝癌发生过程中经典的“卵圆”细胞相似；最终，这些细胞类型在癌前肝细胞结节周围富集。结节内偶尔出现的转化肝细胞表现出强烈的免疫反应性。在肝癌发生的后期，这些抗体对严重腺瘤区域的上皮细胞以及胆管瘤和部分（但不是全部）肝细胞癌的肿瘤上皮细胞进行染色。我们的结果证明了p39在肝癌发生的“卵圆”细胞中的存在，并表明一些转化的肝细胞群体在转化后表现出这种细胞角蛋白。
