Fibroblast-like transformation and c-myc gene alteration of human hepatocytes induced by novobiocin and butyrate.

Topoisomerase II inhibitor novobiocin and deacetylase inhibitor sodium butyrate synergistically transformed Chang liver cells into fibroblast-like cells. In these fibroblast-like cells, the production of type III procollagen was increased and the DNase I hypersensitivity of c-myc gene was reduced. In addition, these changes were associated with an increased acetylation of nuclear proteins, especially those of DNase I sensitive nucleosomes. Therefore, it is suggested that chemical modulation of nuclear proteins by novobiocin and butyrate may be responsible, at least partly, for the alteration of the chromatin structure of c-myc gene and the fibroblast-like transformation of Chang liver cells.