Bisphenol A and its biomaterial monomer derivatives alteration of in vitro cytochrome P450 metabolism in rat, minipig, and human.
Bisphenol A (BPA) is a common structural component in a wide variety of biomaterial monomers. The effects of BPA and the following derivatives: bisphenol A glycidyl methacrylate (BisGMA), bisphenol A glycidyl diacrylate (BAGDA), bisphenol A ethoxylate dimethacrylate (BAEDM), bisphenol A dimethacrylate (BADM), and bisphenol A diglycidyl ether (BADGE) on mixed function oxidases (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 derivatives was used to assess inhibition or stimulation of human, rat (male and female) liver, and minipig liver microsomal MFO activity. For human preparations the strongest inhibition by BPA was observed for CYP 2C. The inhibition was most prominent when a lower dose of BPA was used on the complete post-mitochondrial fraction. BPA inhibited rat microsomal CYP 1A isoform-specific metabolite production to 29 +/- 3% of control levels (100%). Biomaterial monomers exhibited mixed effects. For example, BPA stimulated CYP 4A in pooled human S9 to 129 +/- 1% of control. Also, BADM and BAGDA stimulated CYP 4A to 141% and 142% of control values, respectively.
Cannon
J M
JM
Office of Regulatory Affairs, Kansas City District, Food and Drug Administration, Office, Lenexa, Kansas 66214, USA.
Kostoryz
E
E
Russo
K A
KA
Smith
R E
RE
Yourtee
D M
DM
D000818:Animals; D001559:Benzhydryl Compounds; D002110:Caffeine / Q000737:chemistry; D003374:Coumarins / Q000737:chemistry; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D003640:Dealkylation; D004008:Diclofenac / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013552:Swine; D013556:Swine, Miniature; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D002110:Caffeine; D003374:Coumarins; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D004008:Diclofenac; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds