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Diverse action of acrylamide on cytochrome P450 and glutathione S-transferase isozyme activities, mRNA levels and protein levels in human hepatocarcinoma cells

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Abstract

Humans are exposed to acrylamide in their diet and cigarette smoke. Acrylamide is metabolized into glycidamide by CYP2E1. However, very few studies regarding the effects of acrylamide on cytochrome P450 and Glutathione S-Transferase (GST) isozymes have been pursued. The aim of this study is to elucidate the effects of acrylamide on cytochrome P450 and GST isozymes in HepG2 cell line. Treatment with 1.25 and 2.5 mM acrylamide caused 9.5- and 3.7-fold increases and 4.0- and 3.3-fold increases in CYP1A-associated ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities, respectively. These increases were consistent with increases in mRNA and protein levels of these isozymes. Similarly, CYP2E1-associated aniline 4-hydroxylase (ANH) activity, protein levels, and mRNA levels increased 2.1- and 2.6-fold, 2.4- and 3.2-fold, and 1.4- and 1.9-fold following 1.25 and 2.5 mM acrylamide treatments, respectively. In addition, GST-mu activity was increased 2.4- and 5.1-fold by acrylamide. Moreover, GST-mu mRNA and protein levels increased twofold as a result of acrylamide treatment. In contrast, GST-pi protein and mRNA levels decreased significantly. In conclusion, human cell exposure to acrylamide causes an increase in the levels of carcinogenicity and toxicity and a disturbance in drug metabolism, possibly due to complex effects on P450 and GST isozymes.

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Acknowledgments

This work was supported by a grant from The Scientific and Technological Research Council of Turkey (109 T062). We would also like to thank the Pamukkale University Research Fund (PAU-BAP 2009BSP009).

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The authors have declared that there is no conflict of interest.

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  1. Department of Biology, Pamukkale University, 20070, Denizli, Turkey

    Alaattin Sen, Ozden Ozgun & Sevki Arslan

  2. Biochemistry Graduate Program and Department of Biological Sciences, Middle East Technical University, 06531, Ankara, Turkey

    Emel Arinç

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  1. Alaattin Sen
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Sen, A., Ozgun, O., Arinç, E. et al. Diverse action of acrylamide on cytochrome P450 and glutathione S-transferase isozyme activities, mRNA levels and protein levels in human hepatocarcinoma cells. Cell Biol Toxicol 28, 175–186 (2012). https://doi.org/10.1007/s10565-012-9214-1

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