Toxicological assays for testing effects of an epigenetic drug on development, fecundity and survivorship of malaria mosquitoes.
Toxicological assays for testing effects of an epigenetic drug on development, fecundity and survivorship of malaria mosquitoes.
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DOI：
10.3791/52041
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发表时间：
2015-01
期刊：
影响因子：
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通讯作者：
Atashi Sharma;T. Anderson;I. Sharakhov
中科院分区：
文献类型：
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作者：
Atashi Sharma;T. Anderson;I. Sharakhov
杀虫剂抗药性是疟疾控制项目面临的一个主要问题。蚊子能迅速适应环境的各种变化，使疟疾控制成为热带国家普遍存在的问题。杀虫剂抗性种群的出现要求探索新的药物靶点途径和化合物来控制病媒蚊子。表观遗传药物在癌症研究中已经得到了很好的应用，但对它们对昆虫的影响却知之甚少。本研究为检验3-Deazaneplanocin a （DZNep）对疟疾媒介冈比亚按蚊（Anopheles gambiae）的毒理学效应提供了一个简单的方案。DZNep是一种用于癌症治疗的实验性表观遗传药物。暴露于DZNep的未成熟蚊子死亡率呈浓度依赖性增加，体积减小，而与对照处理相比，该化合物降低了成年蚊子的繁殖力。此外，与对照处理相比，DZNep暴露后蚊子s -腺苷型同型半胱氨酸（SAH）水解酶活性呈药物依赖性下降。这些方案为研究人员提供了一个简单的、逐步的程序来评估一种实验性药物的多个毒理学终点，并反过来展示了一种独特的多管并进的方法，用于探索水溶性表观遗传药物或感兴趣的化合物对媒介蚊子和其他昆虫的毒理学效应。
Insecticidal resistance poses a major problem for malaria control programs. Mosquitoes adapt to a wide range of changes in the environment quickly, making malaria control an omnipresent problem in tropical countries. The emergence of insecticide resistant populations warrants the exploration of novel drug target pathways and compounds for vector mosquito control. Epigenetic drugs are well established in cancer research, however not much is known about their effects on insects. This study provides a simple protocol for examining the toxicological effects of 3-Deazaneplanocin A (DZNep), an experimental epigenetic drug for cancer therapy, on the malaria vector, Anopheles gambiae. A concentration-dependent increase in mortality and decrease in size was observed in immature mosquitoes exposed to DZNep, whereas the compound reduced the fecundity of adult mosquitoes relative to control treatments. In addition, there was a drug-dependent decrease in S-adenosylhomocysteine (SAH) hydrolase activity in mosquitoes following exposure to DZNep relative to control treatments. These protocols provide the researcher with a simple, step-by-step procedure to assess multiple toxicological endpoints for an experimental drug and, in turn, demonstrate a unique multi-prong approach for exploring the toxicological effects of water-soluble epigenetic drugs or compounds of interest against vector mosquitoes and other insects.