title: Biotransformation enzymes and lung cell response to 2-hydroxyethyl-methacrylate.
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 μM) 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 mM 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.
authors: Nordic Institute of Dental Materials AS, PO Box 3874, Ullevaal Stadion, N-0805 Oslo, Norway. j.t.samuelsen@niom.no.
authors: J T
authors: JT
authors: Samuelsen
authors: J A
authors: JA
authors: Holme
authors: M
authors: M
authors: Låg
authors: P E
authors: PE
authors: Schwarze
authors: J E
authors: JE
authors: Dahl
authors: R
authors: R
authors: Becher
mesh_terms: D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D005456:Fluorescent Dyes / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology* / Q000201:enzymology*; D008689:Methacrylates / Q000494:pharmacology*; D008858:Microscopy, Phase-Contrast; D011921:Rats, Inbred WKY; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D005456:Fluorescent Dyes; D008689:Methacrylates; D018336:Receptors, Aryl Hydrocarbon; C005044:hydroxyethyl methacrylate