Evidence for multiple mechanisms of toxicity in larval rainbow trout (Oncorhynchus mykiss) co-treated with retene and α-naphthoflavone
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- 作者：Jason A. Scott ; Peter V. Hodson
- 关键词：Retene ;
; //www.sciencedirect.com/scidirimg/entities/204e.gif"" alt=""greek small letter alpha"" title=""greek small letter alpha"" border=""0"">-Naphthoflavone ; Mechanisms ; CYP1A ; AhR ; Mixture toxicity
- 刊名：Aquatic Toxicology
- 出版年：2008
- 出版时间：7 July 2008
- 年：2008
- 卷：88
- 期：3
- 页码：200-206
- 全文大小：505 K
文摘
Alkylated polycyclic aromatic hydrocarbons, such as retene (7-isopropyl-1-methylphenanthrene), induce cytochrome P450 1A (CYP1A) enzymes and produce dioxin-like toxicity in the embryo–larval stages of fish characterized by the signs of blue sac disease (BSD). The signs of toxicity are well characterized; however, the mechanism is not well understood. To elucidate the role of CYP1A in retene toxicity, larval rainbow trout (Oncorhynchus mykiss) were co-treated with a range of concentrations of ![]()
-naphthoflavone (ANF), a known CYP1A inhibitor. The co-treatment produced synergistic toxicity at 3.2–100 μg/L ANF, after which toxicity at 180 μg/L ANF dropped to levels typical of retene-only. At 320 μg/L ANF, toxicity increased with or without retene, indicating that ANF alone was capable of inducing BSD. In addition, the additive toxicity of retene-only and 320 μg/L ANF-only approximately equalled that of the co-exposed larvae (100 μg/L retene + 320 μg/L ANF), indicating response addition. Thus, two mechanisms of action occurred in co-exposed larvae at different concentrations of ANF. In trout larvae, there was a correlation between toxicity and CYP1A protein concentrations, and in juvenile trout, ANF produced a concentration-dependent inhibition of ethoxyresorufin-O-deethylase (EROD) activity without a measurable drop in CYP1A protein. Taken together, the mechanism underlying the synergistic toxicity is EROD-independent and may be AhR-dependent. This study demonstrated that multiple, exposure-dependent mechanisms can occur in mixture toxicity, suggesting that current risk assessment models may drastically underestimate toxicity, particularly of mixtures containing both CYP1A inducers and inhibitors.