The nonspecific esterases of human mononuclear leukocytes metabolize arylamine carcinogens and steroids esters

The presence of non-specific esterases in various leukocyte subfractions of whole blood is well established, but no endogenous substrates or function for these esterases have been identified. Here we report on the metabolism of N-acetoxy-2-acetylami-nofluorene (NA-AAF) and beclomethasone-17–21-dipropinate (BDP) in viable human mononuclear leukocytes (HML). Conversion of NA-AAF to DNA binding intermediates and BDP to beclomethasone-17-monopropionate by a common esterase was demonstrated and then further characterized by a broad spectrum of effectors including well-established inhibitors and substrates for the nonspecific esterases. Two esters, beta estradiol-17-propionate and alpha naphtyl propionate, competitively inhibited this esterase activity. Together, these data identify at least one isozyme of the A-or B-classes of HML nonspecific esterases as being responsible for the metabolism of NA-AAF and BDP. That HML nonspecific esterases may be functionally involved in arylamine carcinogenesis (i.e. as it may relate to immune function) and in the endogenous production of steroids from their naturally occurring esters emphasizes the importance of continuing their characterization.