Biotransformation enzymes in two renal epithelial cell lines (LLC-PK1 and RK-L).

The activities of smooth endoplasmic reticulum (SER) and cytosolic xenobiotic-metabolizing enzymes were studied in two established renal tubular cell lines, LLC-PK1 and RK-L (rat kidney, Lübeck). The glutathione content in both cell lines was about 20-fold higher than in rat kidney homogenates; this is explained by a 20- to 50-fold lower activity of gamma-glutamyl transpeptidase in the cell lines. Among SER enzymes, the cytochrome P-450-dependent dimethylhydrazine demethylase was in the same range in both cell lines as compared with rat kidney S9 fraction. Pretreatment with phenobarbital (0.1 mM in the culture medium for 3 d) did not induce SER or cytosolic enzyme activities. The glutathione content in both epithelial cell lines can be modified by an inhibitor of GSH synthesis (buthionine sulfoximine, BSO), whereas inhibition of gamma-glutamyl transpeptidase (acivicin) did not significantly increase the GSH-concentration. Despite these biochemical characteristics, the utility of the new RK-L-line needs to be evaluated in experimental studies on renal transport processes and metabolism as well as cytotoxicity and genotoxicity of xenobiotics.