PMID- 26924701 OWN - NLM STAT- MEDLINE DCOM- 20170227 LR - 20190601 IS - 1614-7499 (Electronic) IS - 0944-1344 (Linking) VI - 23 IP - 11 DP - 2016 Jun TI - The effects of CYP1A inhibition on alkyl-phenanthrene metabolism and embryotoxicity in marine medaka (Oryzias melastigma). PG - 11289-11297 LID - 10.1007/s11356-016-6098-2 [doi] AB - 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 alpha-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 mug/L retene with 0, 5, 10, 100, and 200 mug/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 mug/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. FAU - Mu, Jingli AU - Mu J AD - Key Laboratory for Ecological Environment in Coastal Areas (State Oceanic Administration, SOA), National Marine Environmental Monitoring Center, Dalian, 116023, China. FAU - Jin, Fei AU - Jin F AD - Key Laboratory for Ecological Environment in Coastal Areas (State Oceanic Administration, SOA), National Marine Environmental Monitoring Center, Dalian, 116023, China. FAU - Wang, Juying AU - Wang J AD - Key Laboratory for Ecological Environment in Coastal Areas (State Oceanic Administration, SOA), National Marine Environmental Monitoring Center, Dalian, 116023, China. jywang@nmemc.org.cn. FAU - Wang, Ying AU - Wang Y AD - Key Laboratory for Ecological Environment in Coastal Areas (State Oceanic Administration, SOA), National Marine Environmental Monitoring Center, Dalian, 116023, China. FAU - Cong, Yi AU - Cong Y AD - Key Laboratory for Ecological Environment in Coastal Areas (State Oceanic Administration, SOA), National Marine Environmental Monitoring Center, Dalian, 116023, China. LA - eng PT - Journal Article DEP - 20160229 PL - Germany TA - Environ Sci Pollut Res Int JT - Environmental science and pollution research international JID - 9441769 RN - 0 (Benzoflavones) RN - 0 (Petroleum) RN - 0 (Phenanthrenes) RN - 0 (Water Pollutants, Chemical) RN - 0W2D2E1P9Q (retene) RN - 604-59-1 (alpha-naphthoflavone) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) RN - EC 2.5.1.18 (Glutathione Transferase) SB - IM MH - Animals MH - Benzoflavones/pharmacology MH - Cytochrome P-450 CYP1A1/*antagonists & inhibitors MH - Dose-Response Relationship, Drug MH - Embryo, Nonmammalian/abnormalities/*drug effects/enzymology MH - Glutathione Transferase/metabolism MH - Oryzias/embryology/*metabolism MH - Petroleum/analysis/metabolism MH - Phenanthrenes/analysis/pharmacokinetics/*toxicity MH - Water Pollutants, Chemical/analysis/pharmacokinetics/*toxicity OTO - NOTNLM OT - Alkylated polycyclic aromatic hydrocarbons OT - CYP1A activity OT - Marine medaka OT - Metabolism OT - Synergistic toxicity EDAT- 2016/03/01 06:00 MHDA- 2017/02/28 06:00 CRDT- 2016/03/01 06:00 PHST- 2015/10/29 00:00 [received] PHST- 2016/01/11 00:00 [accepted] PHST- 2016/03/01 06:00 [entrez] PHST- 2016/03/01 06:00 [pubmed] PHST- 2017/02/28 06:00 [medline] AID - 10.1007/s11356-016-6098-2 [pii] AID - 10.1007/s11356-016-6098-2 [doi] PST - ppublish SO - Environ Sci Pollut Res Int. 2016 Jun;23(11):11289-11297. doi: 10.1007/s11356-016-6098-2. Epub 2016 Feb 29.