Primary screening and inhibition of macromolecular biosynthesis by benfluron metabolites in vitro

Cytotoxicity and mechanisms of action of 2 metabolites of benfluron (BF), namely 7-dihydrobenfluron (DBF) and benfluron N-oxide (NOBF) were tested. Cytotoxicity in the primary biochemical screening was measured by the inhibition of 14C-adenine and 14C-valine incorporation into the TCA-insoluble fraction of Ehrlich ascites carcinoma (EAC) cells under defined in vitro conditions. Both metabolites were found to have cytotoxic effects, with NOBF being more active than DBF. Further we investigated the kinetics of incorporation not only of adenine and valine, but also of 14C-thymidine and 14C-uridine both into Ehrlich carcinoma cells and into P388 leukemia cells.