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TitleCharacterization of the inhibition of genistein glucuronidation by bisphenol A in human and rat liver microsomes
NameCoughlin, Janis Laura (author), Buckley, Brian (chair), Thomas, Paul E (internal member), Reuhl, Kenneth (internal member), Aleksunes, Lauren (internal member), Rutgers University, Graduate School - New Brunswick,
Degree Date2011-10
Date Created2011
SubjectToxicology,
Genistein,
Bisphenol A ,
Carcinogenesis—Animal models ,
Glucuronides—Synthesis
DescriptionGenistein is a natural phytoestrogen that is found abundantly in the soybean. Bisphenol A (BPA) is a synthetic chemical used in the synthesis of polycarbonate plastics and epoxy resins. Endocrine disrupting properties of both genistein and BPA have been well established by various laboratories. Because the adverse biological effects caused by genistein and BPA are similar, and may include common co-exposure scenarios in the general population such as in the consumption of a soy-milk latte from a polycarbonate plastic coffee mug, analysis of the perturbation of the metabolism via glucuronidation of genistein in the presence of BPA has been assessed. Human and rat liver microsomes were exposed to varying doses of genistein (0 to 250 μM) in the absence (0 μM) or presence (25 μM) of BPA. Treatment with 25 μM BPA caused non-competitive inhibition of the glucuronidation of genistein in human liver microsomes with a Ki value of 58.7 μM, represented by a decrease in Vmax from 0.93 ± 0.10 nmol/min/mg in the absence of BPA to 0.62 ± 0.05 nmol/min/mg in the presence of BPA, and a negligible change in Km values between treatment groups. The addition of BPA to incubations performed in rat liver microsomes resulted in competitive inhibition of the glucuronidation of genistein at a Ki of 35.7 μM; Vmax values remained steady (2.91 ± 0.26 nmol/min/mg in the absence of BPA and 3.05 ± 0.41 nmol/min/mg in the presence of BPA), while Km values increased in the presence of BPA (49.4 ± 14 μM in the absence of BPA and 84.0 ± 28 μM in the presence of BPA). These findings indicate that the type of inhibition on genistein glucuronidation exerted by BPA differs among species.
NoteM.S.
NoteIncludes bibliographical references
Noteby Janis Laura Coughlin
Genretheses
Persistent URLhttp://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000063361
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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