Metabolomics Reveals Target and Off-Target Toxicities of a Model Organophosphate Pesticide to Roach (Rutilus rutilus): Implications for Biomonitoring

详细信息    查看全文

• 作者：Andrew D. Southam ; Anke Lange ; Adam Hines ; Elizabeth M. Hill ; Yoshinao Katsu ; Taisen Iguchi ; Charles R. Tyler ; Mark R. Viant
• 刊名：Environmental Science & Technology
• 出版年：2011
• 出版时间：April 15, 2011
• 年：2011
• 卷：45
• 期：8
• 页码：3759-3767
• 全文大小：911K
• 年卷期：v.45,no.8(April 15, 2011)
• ISSN：1520-5851

文摘

The ability of targeted and nontargeted metabolomics to discover chronic ecotoxicological effects is largely unexplored. Fenitrothion, an organophosphate pesticide, is categorized as a 鈥渞ed list鈥?pollutant, being particularly hazardous to aquatic life. It acts primarily as a cholinesterase inhibitor, but evidence suggests it can also act as an androgen receptor antagonist. Whole-organism fenitrothion-induced toxicity is well-established, but information regarding target and off-target molecular toxicities is limited. Here we study the molecular responses of male roach (Rutilus rutilus) exposed to fenitrothion, including environmentally realistic concentrations, for 28 days. Acetylcholine was assessed in brain; steroid metabolism was measured in testes and plasma; and NMR and mass spectrometry-based metabolomics were conducted on testes and liver to discover off-target toxicity. O-demethylation was confirmed as a major route of pesticide degradation. Fenitrothion significantly depleted acetylcholine, confirming its primary mode of action, and 11-ketotestosterone in plasma and cortisone in testes, showing disruption of steroid metabolism. Metabolomics revealed significant perturbations to the hepatic phosphagen system and previously undocumented effects on phenylalanine metabolism in liver and testes. On the basis of several unexpected molecular responses that were opposite to the anticipated acute toxicity, we propose that chronic pesticide exposure induces an adapting phenotype in roach, which may have considerable implications for interpreting molecular biomarker responses in field-sampled fish.