Chemically induced DNA fragmentation and unscheduled DNA synthesis were determined in gamma-glutamyltranspeptidase (GGT)-positive and GGT-negative hepatocytes isolated from rat livers subjected to a multistage hepatocarcinogenesis regimen (Solt-Farber), which included 0.05% phenobarbital promotion for 6 weeks (early) or 6 months (late). The results indicated that there was DNA damage in untreated GGT-positive and GGT-negative hepatocytes with either period of promotion compared with normal hepatocytes; however, no statistical difference could be seen between GGT-positive and GGT-negative hepatocytes. DNA damage induced in vitro by the activation-dependent carcinogen dimethylnitrosamine was much less in GGT-positive hepatocytes than in GGT-negative hepatocytes or normal hepatocytes. No significant difference in DNA damage was seen in both GGT-positive and GGT-negative cell populations following treatment with the activation-independent carcinogen ethylnitrosourea (ENU), although DNA damage of GGT-positive hepatocytes was less than that of normal hepatocytes. The background of unscheduled DNA synthesis in both GGT-positive and GGT-negative hepatocytes at either time of promotion was higher than that of normal hepatocytes. The capacity for DNA repair in GGT-positive hepatocytes appeared to be lower than that in GGT-negative hepatocytes. GGT-negative hepatocytes exhibited a lower capacity for DNA repair than that of normal hepatocytes in terms of the rate of unscheduled DNA synthesis elicited by dimethylnitrosamine and ethylnitrosourea in vitro.

Serial observations were performed on the sera α-fetoprotein (A F P) as well as on the immunohistochemical localization of A F P in liver tissues during hepatocarcinogenesis induced with 3'-Me-DAB in rats. Results showed that the dynamics of the sera A F P in rats bearing hepatocellular carcinomas (HCC) revealed saddle-like curve, whereas that of those rats without hearing HCC only increased at a sustained low level. The pathological bases which are responsible for precancerous increase of sera AFP are as follows: the small basophilic hepatocytes, "survival" hepatocytes, hyperplastic nodules, dysplastic hepatocytes, the hepacytic cords within the cholangiofibrosis foci. Solt-Farber model analysis indicated that the increase of sera AFP was related to the proliferation of the initiated cells. Immunoelectronic microscopy demonstrated the AFP was located on the membranes, which may be caused by the absorption of AFP from blood onto the cell membranes.