Bisphenol A and its biomaterial monomer derivatives alteration of in vitrocytochrome P450 metabolism in rat, minipig, and human

Bisphenol A (BPA) is a common structural component in a wide variety of bio material monomers. The effects of BPA and the following derivatives: bisphe nol A glycidyl methacrylate (BisGMA), bisphenol A glycidyl diacrylate (BAGD A), bisphenol A ethoxylate dimethacrylate (BAEDM), bisphenol A dimethacryla te (BADM), and bisphenol A diglycidyl ether (BADGE) on mixed function oxida ses (MFOs) are reported in this study. The rate of formation of metabolites from isoform-specific substrates for the MFOs (or cytochromes) CYP 1A, 2A, 2C, 2E, 3A, and 4A in the absence (control) and presence of BPA and deriva tives was used to assess inhibition or stimulation of human, rat (male and female) liver, and minipig liver microsomal MFO activity. For human prepara tions the strongest inhibition by BPA was observed for CYP 2C. The inhibiti on was most prominent when a lower dose of BPA was used on the complete pos t-mitochondrial fraction. BPA inhibited rat microsomal CYP 1A isoform-speci fic metabolite production to 29 +/- 3% of control levels (100%). Biomateria l monomers exhibited mixed effects. For example, BPA stimulated CYP 4A in p ooled human S9 to 129 +/- 1% of control. Also, BADM and BAGDA stimulated CY P 4A to 141% and 142% of control values, respectively.