EVALUATION OF THE XENOBIOTIC BIOTRANSFORMATION CAPABILITY OF 6 RODENTHEPATOMA-CELL LINES IN COMPARISON WITH RAT HEPATOCYTES

Phase I and II activities were examined in six rodent hepatoma cell li nes and compared with these of cultured rat hepatocytes both in basal conditions and after exposure to 5 mu M methylcholanthrene, 2 mM pheno barbital, and 15 mu M beta-naphtoflavone, The metabolic profile of tes tosterone was also studied. The highest aryl hydrocarbon hydroxylase a nd 7-ethoxycoumarin O-deethylase activities were found in MHlCl cells. Comparable values for 7-ethoxyresorufin O-deethylase activity, rangin g from 21.6 to 42.9 pmol/mg X min, were observed in the hepatocytes an d hepatoma cells, except the HTC cells. In contrast, only Fao cells sh owed 7-pentoxyresorufin O-depentylase activity at levels similar to th ose of hepatocytes (6.2 +/- 1.0 and 7.4 +/- 1.2 pmol/mg X min, respect ively). Rat hepatocytes actively hydroxylated p-nitrophenol, but this activity was not measurable in hepatoma cells. Glutathione transferase activity was maintained in ail the hepatoma cell lines at similar lev els to those found in hepatocytes (684 +/- 56 nmol/mg X min). The seve n hydroxylated metabolites of testosterone produced by cultured hepato cytes were negligible in hepatoma cells. Exposure of cells to inducers revealed that aryl hydrocarbon hydroxylase activity was mainly increa sed after treatment with 3-methylcholanthrene and beta-naphtoflavone, and the highest values were found in rat hepatocytes followed by MPlCl and Fao cells. 3-Methylcholanthrene and naphtoflavone treatment also resulted in a marked increase in 7-ethoxyresorufin O-deethylase activi ty in hepatocytes as well as in H4IIC3, McA-Rh7777, MHlCl, and Fao cel ls. An enhancement of 7-ethoxycoumarin O-deethylase activity due to th e three inducers was observed in both rat hepatocytes and hepatoma cel ls, with MHlCl cells heated with methylcholanthrene showing the highes t activity (727 +/- 74 pmol/mg X min). Increases in 7-pentoxyresorufin O-depentylase activity were detected after phenobarbital treatment of hepatocytes, MHlCl, and Fao cells, whereas a low response was observe d in the other hepatoma cells. Of the six hepatoma cell lines examined , MHlCl and Fao cells are the ones that are most similar to cultured r at hepatocytes in their expression of biotransformation activities.