Nuclear Matrix Condensation and c-myc and c-fos Expression Are Specifically Altered in Cultured Rat Hepatocytes after Exposure to Cyproterone Acetate and Phenobarbital

Regenerative or hyperplastic growth promotes carcinogenesis and can be induced by many nongenotoxic carcinogens. The mitogenic potential of the rodent liver tumor promoters, cyproterone acetate and phenobarbital was investigated in primary rat hepatocyte cultures. Two premitotic markers were analyzed, the expression of two immediate-early genes (c-fos and c-myc) and the decrease in the nuclear quinacrine dihydrochloride fluorescence indicative for a G0-G1 cell cycle shift. C-fos expression and decrease in nuclear fluorescence could be induced by both chemicals, phenobarbital being the lesser potent, whereas c-myc expression was only inducible by cyproterone acetate. In situ hybridization with c-myc revealed that both chemicals enhanced c-myc mRNA levels in individual cells, however the number of responding hepatocytes was increased by cyproterone acetate only. The chemical-induced premitotic changes in hepatocytes were highly specific in terms of affected genes and ploidy levels of responding hepatocytes.