Metabolic enzyme induction by HepG2 cells exposed to oxygenated and nonoxygenated polycyclic aromatic hydrocarbons
Metabolic enzyme induction by HepG2 cells exposed to oxygenated and nonoxygenated polycyclic aromatic hydrocarbons
复制标题
DOI：
10.1021/tx060197u
复制
发表时间：
2007-02-01
影响因子：
4.1
通讯作者：
Matsuda, Tomonari
中科院分区：
文献类型：
--
作者：
Misaki, Kentaro;Matsui, Saburo;Matsuda, Tomonari
大气环境中富含含氧多环芳烃(Oxy-PAHs)，如多环芳酚、多环芳酮以及多环芳烃(PAHs)。本研究详细研究了13种多环芳烃和7种氧基多环芳烃对人肝癌细胞P4501A1、1A2和1B1、醛酮还原酶1c1、NAD(P)H依赖的苯醌氧化还原酶1和谷胱甘肽S转移酶M1等6种代谢酶基因的诱导作用。大多数多环芳烃，如苯并[a]芘(B[a]P)，对P4501A1和1A2的诱导作用较强，而氧基多环芳烃，如5，12-萘醌(NCQ)和11H-苯并[b]-11-酮(B[b]FO)的诱导作用较弱。氧-多环芳烃、11H-苯并[a]荧烯-11-酮(B[a]FO)、NCQ、环戊二烯-3(4H)-酮(CPPO)和B[b]FO以及P450s诱导的多环芳烃如B[a]P、苯并[k]荧菲(B[k]FA)和二苯并[a，h]菲(DB[a，h]A)也能显著诱导AKR1C1mRNA的表达。NQO1mRNA的化学依赖和时间依赖诱导模式均为P4501A1和AKR1C1混合型。暴露于多环芳烃B[a]P和B[k]FA后，GSTM1mRNA有下降的趋势。
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.