Dissertation/ Thesis

Down-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell Lines

التفاصيل البيبلوغرافية
العنوان: Down-regulation of Cytochrome P450 2C8 by 3-methylcholanthrene in Human Hepatocellualar Carcinoma Cell Lines
المؤلفون: Utgikar, Rucha
Thesis Advisors: Riddick, David S.
سنة النشر: 2012
المجموعة: University of Toronto
مصطلحات موضوعية: drug metabolism, CYP2C8
Time: 0419
الوصف: 3-Methylcholanthrene (MC) is a model polycyclic aromatic hydrocarbon that induces cytochrome P450 1A1 (CYP1A1) expression. This laboratory has shown previously that aromatic hydrocarbons, which are important environmental toxicants, down-regulate the expression of rat liver CYP2C11. Recent observations also suggested that CYP2C8, a human enzyme that metabolizes antineoplastic and antidiabetic drugs, among others, is down-regulated in response to aromatic hydrocarbon exposure in primary human hepatocytes. I examined the regulation of CYP2C8 at the mRNA level by MC in two human hepatocellular carcinoma cell lines, HepG2 and HepaRG. MC down-regulated CYP2C8 mRNA levels in HepG2 cells at 24 hours and in HepaRG cells at 48 hours. CYP1A1 mRNA was induced by MC in both cell lines and HepaRG cells appeared to be more sensitive than HepG2 cells to MC-induced cytotoxicity. Further studies are warranted to define the mechanisms and functional impacts of the modulation of this important human CYP by environmental toxicants.
Original Identifier: oai:tspace.library.utoronto.ca:1807/32636
نوع الوثيقة: Thesis
الاتاحة: http://hdl.handle.net/1807/32636
رقم الانضمام: edsndl.TORONTO.oai.tspace.library.utoronto.ca.1807.32636
قاعدة البيانات: Networked Digital Library of Theses & Dissertations