Comparative study of CYP1A1 induction by 3-methylcholanthrene in various human hepatic and epidermal cell types

Toxicology in Vitro : an International Journal Published in Association with BIBRA
C DelescluseR Rahmani

Abstract

Hepatocytes and keratinocytes are among the most widely used cells in pharmaco-toxicology, but a limitation of these models is the provision of human tissues on a regular basis. The suitability of HepG2, HaCaT and HESV cell lines as an acceptable substitute for primary cultures was examined. In these cell types, the effects of 3-methylcholanthrene (3-MC) were analysed on CYP1A1 gene expression, a crucial CYP subfamily in the activation of chemical carcinogens. Ethoxyresorufin O-deethylase (EROD) activity was never detected in HESV cells, but in other cell types it was stimulated in a concentration-dependent manner (maximal induction, 1-2.5 mum). Above this peak induction the effect fell rapidly. Northern blot analysis of CYP1A1 mRNA agreed with the trends obtained for EROD values. However, the decrease of the EROD activity observed at the highest 3-MC concentrations was not correlated with CYP1A1 mRNA reduction. This study also demonstrated that 3-MC is capable of significantly inducing CYP1A1 in HaCaT cells (17-fold over control), as in human hepatocytes (six- to 18-fold) and HepG2 (fourfold). Therefore, in contrast to SV40-immortalized keratinocytes (HESV), spontaneously immortalized keratinocytes (HaCaT) may constitute a val...Continue Reading

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Citations

May 8, 2010·Archives of Toxicology·Thomas Haarmann-StemmannJosef Abel
Nov 25, 2000·Toxicology·C DelescluseR Rahmani
Jun 15, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lucie StejskalovaPetr Pavek
Mar 30, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nicola J HewittStefan Pfuhler
Jul 30, 2011·Biomicrofluidics·Junji Fukuda, Kohji Nakazawa
Nov 27, 2008·Bulletin of Environmental Contamination and Toxicology·G H LuZ Zhu
Feb 7, 2012·Mutation Research·Zuzana ValovičováAlena Gábelová
Nov 1, 2009·Environmental Toxicology and Pharmacology·Chao WangPeifang Wang
May 10, 2017·Genetics and Molecular Biology·Grazyelle Sebrenski da SilvaVera Maria Fonseca de Almeida E Val

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