Metabolic enzyme induction by HepG2 cells exposed to oxygenated and nonoxygenated polycyclic aromatic hydrocarbons.
Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) such as polycyclic aromatic quinones and polycyclic aromatic ketones as well as polycyclic aromatic hydrocarbons (PAHs) are abundant in the atmospheric environment. In this study, mRNA induction of six metabolic enzymes including P4501A1, 1A2, and 1B1, aldo-keto reductase 1C1 (AKR1C1), NAD(P)H-dependent quinone oxidoreductase 1 (NQO1), and glutathione S-transferase M1 (GSTM1) were examined in detail in human hepatoma (HepG2) cells exposed to environmentally relevant 13 PAHs and seven oxy-PAHs. Most PAHs such as benzo[a]pyrene (B[a]P) showed significant induction of P4501A1 and 1A2 mRNA, while induction by oxy-PAHs such as 5,12-naphthacenequinone (NCQ) and 11H-benzo[b]fluoren-11-one (B[b]FO) occurred less strongly. AKR1C1 mRNA was significantly induced by oxy-PAHs, 11H-benzo[a]fluoren-11-one (B[a]FO), NCQ, cyclopenta[cd]pyren-3(4H)-one (CPPO), and B[b]FO and also by P450s-inducing PAHs such as B[a]P, benzo[k]fluoranthene (B[k]FA), and dibenz[a,h]anthracene (DB[a,h]A). Both chemical-dependent and time-dependent induction patterns of NQO1 mRNA were of the mixed types of P4501A1 and AKR1C1. The tendency for the decrease of GSTM1 mRNA was observed when exposed to PAHs B[a]P and B[k]FA.
Misaki
Kentaro
K
Department of Environmental Engineering and Graduate School of Global Environmental Studies, Kyoto University, Yoshidahonmachi, Kyoto 606-8501, Japan.
Matsui
Saburo
S
Matsuda
Tomonari
T
D015089:20-Hydroxysteroid Dehydrogenases / Q000187:drug effects* / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects / Q000378:metabolism; D001711:Biotransformation / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000187:drug effects / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005982:Glutathione Transferase / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000187:drug effects* / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000493:pharmacokinetics*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors
D015089:20-Hydroxysteroid Dehydrogenases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; C115140:3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase; C585496:CYP1B1 protein, human; C447479:NQO1 protein, human