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在斑马鱼(Danio rerio)幼虫中进行分子和行为评估,以研究环境相关水平的抗癌药物环磷酰胺暴露后的情况。

Molecular and behavioral assessment in larval zebrafish (Danio rerio) following exposure to environmentally relevant levels of the antineoplastic cyclophosphamide.

机构信息

Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, University of Florida, Gainesville, FL 32611, USA.

Center for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, UF Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, University of Florida, Gainesville, FL 32611, USA.

出版信息

Environ Toxicol Pharmacol. 2022 Feb;90:103809. doi: 10.1016/j.etap.2022.103809. Epub 2022 Jan 13.

DOI:10.1016/j.etap.2022.103809
PMID:35033682
Abstract

Antineoplastics treat cancers and enter aquatic ecosystems through wastewater and hospital effluent. Risks associated with antineoplastics are not well characterized in aquatic organisms. We conducted zebrafish embryo/larvae toxicity assays to evaluate responses to cyclophosphamide (0.01-50 µM). Zebrafish survival was affected by 5 µM cyclophosphamide and deformities were noted at > 1 µM. Oxidative respiration remained unchanged in embryos with exposure up to 200 µM. Reactive oxygen species were not increased by 50 µM cyclophosphamide exposure. More than 15 oxidative stress and immune-related transcripts were measured. Superoxide dismutase 2 and heat shock protein 70 and 90a were induced in larvae by cyclophosphamide. Immune-related transcripts were assessed due to immunosuppressive properties of cyclophosphamide, and mmp9 and myd88 levels were altered in expression. Hyperactivity of larvae was noted following 5 µM cyclophosphamide exposure. There was no change in anxiety-related endpoints (light-dark preference). Risks for larval fish exposed to cyclophosphamide in the environment may be low.

摘要

抗肿瘤药物通过废水和医院污水治疗癌症并进入水生生态系统。水生生物体内抗肿瘤药物的风险特征尚未得到很好的描述。我们进行了斑马鱼胚胎/幼虫毒性试验,以评估环磷酰胺(0.01-50 μM)的反应。5 μM 环磷酰胺会影响斑马鱼的存活,而> 1 μM 则会出现畸形。暴露于高达 200 μM 的环磷酰胺时,胚胎的氧化呼吸保持不变。50 μM 环磷酰胺暴露不会增加活性氧。测量了超过 15 种氧化应激和免疫相关转录本。环磷酰胺诱导幼虫中超氧化物歧化酶 2 和热休克蛋白 70 和 90a 的表达。由于环磷酰胺具有免疫抑制特性,因此评估了免疫相关转录本,并且 mmp9 和 myd88 水平的表达发生了改变。5 μM 环磷酰胺暴露后,幼虫表现出过度活跃。与焦虑相关的终点(明暗偏好)没有变化。暴露于环境中环磷酰胺的幼鱼的风险可能较低。

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