Effects of barbiturates with or without liver-tumor-promoting activity on survival and DNA synthesis of suckling and adult rat hepatocytes in serum-free primary culture

The effects of four barbiturates with or without liver-tumor-promoting activity were examined on survival and deoxyribonucleic acid (DNA) synthesis of suckling and adult rat, hepatocytes in serum-free primary culture. Of the four barbiturates, two promoters, phenobarbital and barbital, enhanced DNA synthesis of suckling rat hepatocytes at low concentrations of 0.5–2 mM or 0.5 mM, but suppressed it at high concentrations of 3 mM or 1.5–4 mM. DNA synthesis of adult rat hepatocytes was, however, only suppressed by phenobarbital within the dose range tested of 1–3 mM. On the other hand, two remaining non-promoters, barbituric acid and amobarbital, did not increase but only suppressed DNA synthesis of suckling rat hepatocytes within the dose ranges of 0.5–4 mM and 0.05–0.5 mM respectively. Phenobarbital and amobarbital were effective for supporting survival and maintaining morphological features of suckling and adult rat hepatocytes at the relatively high concentrations of 3–4 mM and 0.5–0.75 mM respectively. However, barbital and barbituric acid were ineffective for maintenance of hepatocytes. The results show that the ability to support survival of primary cultured hepatocytes is not a common property of liver-tumor-promoter barbiturates but is a common property of some barbiturates with high lipophilicity and that the maintenance of hepatocytes by phenobarbital or amobarbital is not due to a counterbalance of stimulated proliferation and death of the cells.