title: Diverse action of acrylamide on cytochrome P450 and glutathione S-transferase isozyme activities, mRNA levels and protein levels in human hepatocarcinoma cells.
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.
authors.affiliation: Department of Biology, Pamukkale University, 20070, Denizli, Turkey.
authors.forename: Alaattin
authors.initials: A
authors.lastname: Sen
authors.forename: Ozden
authors.initials: O
authors.lastname: Ozgun
authors.forename: Emel
authors.initials: E
authors.lastname: Arinç
authors.forename: Sevki
authors.initials: S
authors.lastname: Arslan
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000815:Aniline Hydroxylase / Q000235:genetics / Q000378:metabolism; D015197:Carcinogenicity Tests; D002470:Cell Survival; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D057075:Enzyme Assays; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D018675:Toxicity Tests
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D020106:Acrylamide; D003577:Cytochrome P-450 Enzyme System; C076307:methoxyresorufin-O-demethylase; D019392:Cytochrome P-450 CYP2E1; D000815:Aniline Hydroxylase; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase