Application of a Genotypic Marker for Analysis of Chemically-Induced Hepatic Carcinogenesis in Rats : Transplantation of Putative Preneoplastic Hepatocytes of Analbuminemic Rats in the Liver of Rats with Normal Albumin Producing Capability

Preneoplastic and neoplastic hepatocytes including hepatocellular carcinomas are immunohistochemically negative for albumin in the liver of analbuminemic rats (NAR). Albumin negative hyperplastic nodules were induced in the livers of NAR. The nodule cells were isolated and transplanted to the livers of F1 hybrids of Sprague-Dawley×NAR (SD×NARF1) by infusion into the mesenteric vein. Since the analbuminemia of NAR is inherited as a recessive trait, the liver of SD×NARF1 retains its capability of producing albumin. Therefore, this system makes it possible to distinguish transplanted nodule cells from the surrounding liver using albumin as a genotypic marker. Ten to 13 days after the infusion, numerous albumin (-) nodules were formed within the albumin (+) livers of the hosts which were being subjected to dietary treatment of 2-acetylaminofluorene plus partial hepatectomy. Of the albumin (-) nodules, 98% were immunohistochemically positive for placental form of glutathione S-transferase (GST-P), which is one of the conventional biochemical markers for nodules. Eight weeks after the infusion, almost the same number of albumin (-) nodules were observed per cm2 of the cross section of the livers as seen on the 10-13 day. Of the albumin (-) nodules, 57% were negative for GST-P indicating that more than half of the nodules changed to phenotypically normal after cessation of the promoting stimulus. This system seems useful to analyze the sequential events during hepatocarcinogenesis using a genotypic marker