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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Authors: | Alaattin Sen Ozden Ozgun Emel Arinç Sevki Arslan |
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Institution: | (1) Department of Biology, Pamukkale University, 20070 Denizli, Turkey;(2) Biochemistry Graduate Program and Department of Biological Sciences, Middle East Technical University, 06531 Ankara, Turkey; |
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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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