Phenobarbital and some other liver tumor promoters stimulate DNA synthesis in cultured rat hepatocytes.

Hepatocytes isolated from normal adult rats were maintained at sub-confluent density in a defined medium in primary culture. In control cultures with added epidermal growth factor and low concentrations of dexamethasone, the rate of DNA synthesis was initially low but increased after about 30 hours in culture. Addition of the xenobiotic liver tumor promoters phenobarbital, alpha-hexachlorocyclohexane or p,p'-dichlorodiphenyltrichloroethane to cultures after cell attachment caused concentration-dependent stimulation of DNA synthesis measured after 2 days in culture. While dexamethasone (30 nM) alone had little effect on hepatocyte DNA synthesis, the stimulatory effects of the xenobiotics required the permissive presence of the steroid.