Mu Jingli, Jin Fei, Wang Juying, Wang Ying, Cong Yi
Key Laboratory for Ecological Environment in Coastal Areas (State Oceanic Administration, SOA), National Marine Environmental Monitoring Center, Dalian, 116023, China.
Environ Sci Pollut Res Int. 2016 Jun;23(11):11289-11297. doi: 10.1007/s11356-016-6098-2. Epub 2016 Feb 29.
Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are the predominant form of PAHs in crude oils, of which, 3-5 ring alkyl-PAH may cause dioxin-like toxicity to early life stages of fish. Retene (7-isopropyl-1-methylphenanthrene), a typical alkyl-phenanthrene compound, can be more toxic than phenanthrene, and the mechanism of retene toxicity is likely related to its rapid biotransformation by cytochrome P450 (CYP) enzymes to metabolites with a wide array of structures and potential toxicities. Here, we investigated how α-naphthoflavone (ANF), a cytochrome P450 1A (CYP1A) inhibitor, affected the embryotoxicity of retene and the role that CYP1A inhibition may play in the interactions. Marine medaka (Oryzias melastigma) embryos were exposed, separately or together, to 200 μg/L retene with 0, 5, 10, 100, and 200 μg/L ANF for 14 days. The results showed that ANF significantly inhibited the induction of CYP1A activity by retene; however, ANF interacted with retene to induce significant developmental toxicity and genotoxicity at 10, 100, and 200 μg/L (p < 0.01). Tissue concentrations of retene and its metabolites and lipid hydroperoxide (LPO) activity also increased, whereas the inhibition of the glutathione S-transferase (GST) activity and the alteration in metabolic profiles of retene were observed. The interactions of retene with ANF indicate that CYP1A inhibition was possibly act through different mechanisms to produce similar developmental effects and genotoxicity. Retene metabolites and altered metabolic profile were likely responsible for retene embryotoxicity to marine medaka. Therefore, elevated toxicity of alkyl-phenanthrene under CYP1A inhibitor suggested that the ecotoxicity of PAHs in coastal water may have underestimated the threat of PAHs to fish or ecosystem.
烷基化多环芳烃（alkyl - PAHs）是原油中多环芳烃的主要存在形式，其中，3 - 5环的烷基化多环芳烃可能会对鱼类的早期生命阶段产生类二噁英毒性。惹烯（7 - 异丙基 - 1 - 甲基菲）是一种典型的烷基菲化合物，其毒性可能比菲更强，惹烯毒性的机制可能与其被细胞色素P450（CYP）酶快速生物转化为具有多种结构和潜在毒性的代谢产物有关。在此，我们研究了细胞色素P450 1A（CYP1A）抑制剂α - 萘黄酮（ANF）如何影响惹烯的胚胎毒性以及CYP1A抑制在这些相互作用中可能发挥的作用。将海洋青鳉（Oryzias melastigma）胚胎分别或同时暴露于含有0、5、10、100和200μg/L ANF的200μg/L惹烯中，持续14天。结果表明，ANF显著抑制了惹烯对CYP1A活性的诱导；然而，在10、100和200μg/L时，ANF与惹烯相互作用会诱导显著的发育毒性和遗传毒性（p < 0.01）。惹烯及其代谢产物的组织浓度以及脂质过氧化（LPO）活性也有所增加，同时观察到谷胱甘肽S - 转移酶（GST）活性受到抑制以及惹烯代谢谱发生改变。惹烯与ANF的相互作用表明，CYP1A抑制可能通过不同机制产生相似的发育效应和遗传毒性。惹烯代谢产物和改变的代谢谱可能是惹烯对海洋青鳉胚胎毒性的原因。因此，CYP1A抑制剂作用下烷基菲毒性的升高表明，沿海水域中多环芳烃的生态毒性可能低估了多环芳烃对鱼类或生态系统的威胁。
