Enhanced sensitivity of perifused primary rat hepatocytes to mitogens and growth modulation by carcinogens

Comparison of stationary cultivation (repeated changes of medium) with perifusion (continuous flow of medium) revealed that perifused hepatocytes show enhanced basal proliferation and are more sensitive to insulin and EGF. Similarly, the sensitivity of bromodeoxyuridine incorporation to inhibition by 3-methylcholanthrene and 2-acetylaminofluorene was increased approximately five-fold and 50-fold, respectively, in perifused hepatocytes, whereas the general toxicity of these compounds was not enhanced. The increase in sensitivity may be due to physical (establishment of steady-state concentrations) and physiological advantages (enhanced biotransformation) of the perifusion culture. Phenobarbital at 100 mum did not affect the labelling indices in either culture system. These results suggest that perifusion is a more suitable culture system for detecting chemicals that modulate hepatocyte growth and for determining their relative potency.