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.