Rat Alloantigens as Cellular Markers for Hepatocytes in Genotypic Mosaic Livers During Chemically Induced Hepatocarcinogenesis

Abstract

Genotypic mosaic rat livers were constructed by intravenous transplantation of carcinogen-altered F344 donor liver cells into livers of (WF × F344)F₁ host rats. Donor rats were treated with a carcinogenic regimen consisting of diethylnitrosamine (200 mg/kg i.p.), followed by an experimental regimen of dietary 0.02% 2-acetylaminofluorene (AAF) and two-thirds partial hepatectomy (PH) (AAF/PH regimen). Host rats received the AAF/PH regimen in addition to transplanted donor liver cells. Utilizing alloantiserum specific for the WF major histocompatibility complex haplotype, RT1^u, 97% of the γ-glutamyltranspeptidase-positive (GT⁺) liver colonies detected in cryostat sections of host rat livers 10–13 days after transplantation were shown to be of F344 donor origin (Hunt et al., Cancer Research, 42:227–236, 1982). Hepatocytes isolated from such genotypic mosaic livers were stained in suspension histochemically and with alloantisera by indirect immunofluorescence to localize GT₊ phenotype and fluorescence in individual hepatocytes: 97% of GT⁺ hepatocytes were of F344 origin, consistent with the cryostat section results. Hepatocellular carcinomas arising in genotypic mosaic host rat livers 17 months after donor liver cell transplantation are presently being typed with alloantisera to establish the donor or host origin of the tumor cells.