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 phenobarbita l 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 dihydrochlor ide fluorescence indicative for a G(0)-G(1) cell cycle shift. C-fos ex pression and decrease in nuclear fluorescence could be induced by both chemicals, phenobarbital being the lesser potent, whereas c-myc expre ssion 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 in creased by cyproterone acetate only. The chemical-induced premitotic c hanges in hepatocytes were highly specific in terms of affected genes and ploidy levels of responding hepatocytes. (C) 1995 Academic Press, Inc.