Institut National de La Recherche Scientifique (INRS), Centre Eau Terre Environnement (ETE), Quebec City, QC, Canada.
Ministère de l'Environnement, de la Lutte Contre les Changements Climatiques, de la Faune et des Parcs (MELCCFP), Centre d'expertise en analyse environnementale du Québec (CEAEQ), Quebec city, QC, Canada.
Bull Environ Contam Toxicol. 2024 Apr 21;112(5):66. doi: 10.1007/s00128-024-03896-9.
In this study, the toxicogenomic effects of five cytostatics (tamoxifen, methotrexate, capecitabine, cyclophosphamide, and ifosfamide) on fathead minnow (Pimephales promelas) larvae were evaluated. Post-fertilization eggs were exposed to increasing concentrations of the drugs for six days. The expression levels of two genetic biomarkers for toxicity and four thyroid hormone-related gene pathways were measured. Interestingly, the results showed that all concentrations of the five cytostatics affect the transcription levels of both toxicity biomarker genes. Additionally, the thyroid hormone-related genes had different expression levels than the control, with the most significant changes observed in those larvae exposed to cyclophosphamide and ifosfamide. While a previous study found no effects on fish morphology, this study suggests that the five cytostatics modify subtle molecular responses of P. promelas, highlighting the importance of assessing multibiological level endpoints throughout the lifecycle of animals to understand the full portrait of potential effects of cytostatics and other contaminants.
本研究评估了五种细胞抑制剂（他莫昔芬、甲氨蝶呤、卡培他滨、环磷酰胺和异环磷酰胺）对黑头软口鲦（Pimephales promelas）幼虫的毒代动力学效应。受精后的卵子暴露于逐渐增加的药物浓度下持续六天。测量了两个毒性生物标志物基因和四个甲状腺激素相关基因途径的表达水平。有趣的是，结果表明五种细胞抑制剂的所有浓度都影响了两个毒性生物标志物基因的转录水平。此外，甲状腺激素相关基因的表达水平与对照组不同，在暴露于环磷酰胺和异环磷酰胺的幼虫中观察到最显著的变化。虽然之前的研究没有发现对鱼类形态的影响，但本研究表明，五种细胞抑制剂改变了黑头软口鲦的细微分子反应，强调了在动物的整个生命周期中评估多生物学水平终点以了解细胞抑制剂和其他污染物潜在影响的全貌的重要性。
