GenX Inhibits P-glycoprotein and Breast Cancer Resistance Protein Transport Activity and Expression at the Blood-Brain Barrier in Sprague-Dawley Rats

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  • March 21, 2019
Creator
  • Richards, Alicia
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
Abstract
  • GenX (CAS No. 62037-80-3) is a replacement for perfluorooctanoic acid (PFOA) as a chemical precursor in fluoropolymer manufacturing. The compound is a persistent contaminant in drinking water and air. To address the potential for CNS toxicity, we investigated the effects of low concentrations (0.01 – 1000 nM) of GenX on ATP-Binding Cassette transporter activity and expression at the blood-brain barrier. Using an ex vivo steady-state luminal fluorescence-based assay, we found that 1 - 1000 nM GenX rapidly inhibited P-glycoprotein (P-gp, ABCB1) and Breast Cancer Resistance Protein (BCRP, ABCG2) activity in SD rats and in human ovarian cancer cells. Inhibition of efflux transport reduces the neuroprotective function of the BBB, potentially exposing the CNS to toxic substrates. If GenX has a similar effect in other P-gp- and BCRP-expressing tissues, then changes in pharmacokinetics of xenobiotics could occur.
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  • In Copyright
Advisor
  • Birnbaum, Linda
  • Cannon, Ronald
  • Ball, Louise
Degree
  • Master of Science
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2018
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