Abstract
A rapid increase in the fraction of small liver cells was observed in the liver of rats during the early stage of hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). The change in cell population was represented by the decrease in glucose-6-phosphatase activity and by the increase in number of gamma-glutamyltranspeptidase-positive cells. When DNA synthesis of liver cells from rats fed 3'-Me-DAB was measured by autoradiography in primary culture, it began to increase 2 weeks after the start of the carcinogen feeding, reaching a plateau level after 3 weeks. Liver cells from rats fed 3'-Me-DAB for 2 weeks or over demonstrated a remarkable resistance to the cytotoxic effect of the carcinogen (0.24 mM) in primary culture. Furthermore, liver cells from rats fed 3'-Me-DAB for 3 weeks or over proliferated in the presence of the carcinogen in primary culture. When liver cells from 3'-Me-DAB-fed and control rats were transplanted into syngeneic rat spleens, the former cells proliferated more vigorously than did the latter. The growth potential of liver cells from 3'-Me-DAB-fed rats tended to be enhanced with time in the carcinogen feeding. Hepatocellular carcinomas developed in the host spleens implanted with liver cells from a rat fed 3'-Me-DAB for 8 weeks. As described above, liver cells from rats fed 3'-Me-DAB demonstrated much greater proliferative ability than normal control cells in vivo and in vitro.