DNA-PLOIDY ANALYSIS OF HEPATIC PRENEOPLASTIC AND NEOPLASTIC LESIONS IN WOODCHUCKS EXPERIMENTALLY INFECTED WITH WOODCHUCK HEPATITIS-VIRUS

We analyzed the DNA ploidy and the nuclear size of hepatocytes within hepatocellular carcinoma, putative preneoplastic (clear cell and basop hilic foci) and adjacent non-neoplastic liver in 30 woodchucks neonata lly infected with the woodchuck hepatitis virus. In livers from contro l woodchucks, in clear cell foci and in most chronic portal hepatitis, the hepatocytes were diploid, with less than 10% tetraploid cells. An euploid peaks were found in 50% of the livers with chronic active hepa titis, in 63% of basophilic foci and in 90% of hepatocellular carcinom a. Within the same tumor, aneuploid peaks with different DNA indices w ere observed frequently, indicating heterogeneity of tumor. S-phase wa s always elevated, indicating an increased rate of proliferation Aneup loid cells had nuclei that were larger than those of control liver cel ls. In some basophilic foci and in some livers with chronic active hep atitis, abnormal DNA was demonstrated before the development of hepato cellular carcinoma, suggesting that these may be populations of hepato cytes at risk of neoplastic transformation.