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Biotransformation enzymes and lung cell response to 2‐hydroxyethyl‐methacrylate
Author(s) -
Samuelsen J. T.,
Holme J. A.,
Låg M.,
Schwarze P. E.,
Dahl J. E.,
Becher R.
Publication year - 2012
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.33287
Subject(s) - aryl hydrocarbon receptor , cytochrome p450 , reactive oxygen species , enzyme , microbiology and biotechnology , biology , biochemistry , in vitro , gene , transcription factor
Abstract The aim of this in vitro study was to investigate possible involvement of cytochrome P450 (CYP) enzymes in modifying the toxic potential of 2‐hydroxyethyl‐methacrylate (HEMA). Primary cultures of CYP expressing rat alveolar type 2 cells were exposed to varying concentrations of HEMA. Nuclear translocation of aryl hydrocarbon receptor (AhR) after HEMA exposure (100 μ M ) was demonstrated by immunocytochemical staining. Using reverse transcriptase PCR, increased mRNA level of AhR‐regulated genes encoding enzymes associated with detoxification of xenobiotics were found. Exposure to 1 m M HEMA rapidly (6 h) resulted in cells with an apoptotic like morphology as suggested by marked nuclear condensation. Cotreatment of the HEMA exposed cells with a CYP inhibitor (disulfiram) or an antioxidant (vitamin C) effectively rescued the cells from this fate. Despite this effect of vitamin C, no increased level of reactive oxygen species was observed in the HEMA exposed cells. Our results suggest that HEMA activates AhR regulated gene transcription and that CYP is involved in the formation of a highly reactive HEMA metabolite. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012.