Mechanism of Circadian Susceptibility to Pesticides

昼夜节律对农药的敏感性机制

• 批准号: 7157907
• 负责人: LOUISA A HOOVEN
• 金额: $ 5万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2009-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7157907
• 关键词: Drosophilidae; animal mortality; arthropod genetics; circadian rhythms; environmental exposure; environmental toxicology; gene environment interaction; gene expression; genetic susceptibility; mutant; pesticides; postdoctoral investigator; pyrethroid; toxin; toxin metabolism

DESCRIPTION (provided by applicant): Circadian clocks allow organisms to adapt biochemical and physiological processes to their environment in rhythms entrained by the solar day. There is intriguing evidence that the toxicological response to a number of xenobiotic compounds varies with time of day in many species, including humans. From these reports, it can be inferred that organisms may protect themselves from environmental toxins by increasing molecular defenses when daily exposure is most expected. We will test this novel hypothesis by monitoring mortality of Drosophila melanogaster exposed to pyrethroids at different times of day. Preliminary microarray data have revealed putative rhythmic expression patterns in genes responsible for detoxifying pyrethroids. We will characterize these patterns and examine the involvement of these genes in rhythmic susceptibility to pyrethroids. Using the tools of systems biology, existing microarray data, and our own results, we will construct a model of the convergence of circadian and toxicological networks in order to highlight common regulatory mechanisms. Humans are inevitably exposed to pyrethroids and other pesticides, and this interdisciplinary investigation is likely to lead to novel strategies protective of human health.

描述（由申请人提供）：昼夜节律允许生物体在太阳日之前夹带的节奏中将生化和生理过程适应其环境。有有趣的证据表明，对许多物种（包括人类）的毒理学反应随着一天中的一天的时间而变化。从这些报告中可以推断出，当每天暴露最期待时，生物体可以通过增加分子防御能力来保护自己免受环境毒素的侵害。我们将通过监测一天中不同时间暴露于拟除虫菊酯的果蝇的死亡率来检验这一新的假设。初步的微阵列数据揭示了负责排毒拟除虫菊酯的基因中假定的节奏表达模式。我们将表征这些模式，并检查这些基因在节奏对拟除虫菊酯的敏感性中的参与。使用系统生物学，现有的微阵列数据和我们自己的结果的工具，我们将构建昼夜节律和毒理网络收敛的模型，以突出共同的监管机制。人类不可避免地暴露于拟除虫菊酯和其他农药中，这种跨学科的调查很可能导致保护人类健康的新策略。