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, a...

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Bibliographic Details
Published in:Chemical research in toxicology 2007-02, Vol.20 (2), p.277-283
Main Authors: Misaki, Kentaro, Matsui, Saburo, Matsuda, Tomonari
Format: Article
Language:English
Subjects:
20-Hydroxysteroid Dehydrogenases - drug effects
20-Hydroxysteroid Dehydrogenases - metabolism
Aryl Hydrocarbon Hydroxylases - drug effects
Aryl Hydrocarbon Hydroxylases - metabolism
Biotransformation - drug effects
Carcinoma, Hepatocellular - metabolism
Cell Line, Tumor
Cytochrome P-450 CYP1A1 - drug effects
Cytochrome P-450 CYP1A1 - metabolism
Cytochrome P-450 CYP1A2 - drug effects
Cytochrome P-450 CYP1A2 - metabolism
Cytochrome P-450 CYP1B1
Cytochrome P-450 Enzyme System - drug effects
Cytochrome P-450 Enzyme System - metabolism
Dose-Response Relationship, Drug
Enzyme Induction - drug effects
Glutathione Transferase - drug effects
Glutathione Transferase - metabolism
Humans
Molecular Structure
NAD(P)H Dehydrogenase (Quinone) - drug effects
NAD(P)H Dehydrogenase (Quinone) - metabolism
Polycyclic Aromatic Hydrocarbons - metabolism
Polycyclic Aromatic Hydrocarbons - pharmacokinetics
RNA, Messenger - drug effects
RNA, Messenger - metabolism
Structure-Activity Relationship
Time Factors
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Summary: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.
ISSN:0893-228X
1520-5010
DOI:10.1021/tx060197u