Division of Environmental Science and Ecological Engineering, Korea University , 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
Environ Sci Technol. 2016 Sep 6;50(17):9689-96. doi: 10.1021/acs.est.6b02751. Epub 2016 Aug 19.
The internal concentration of chemicals in exposed organisms changes over time due to absorption, distribution, metabolism, and excretion processes since chemicals are taken up from the environment. Internal concentration and time are very important modifiers of toxicity when biomarkers are used to evaluate the potential hazards and risks of environmental pollutants. In this study, the responses of molecular biomarkers, and the fate of chemicals in the body, were comprehensively investigated to determine cause-and-effect relationships over time. Chlorpyrifos (CP) was selected as a model chemical, and Caenorhabditis elegans was exposed to CP for 4 h using the passive dosing method. Worms were then monitored in fresh medium during a 48-h recovery regime. The mRNA expression of genes related to CYP metabolism (cyp35a2 and cyp35a3) increased during the constant exposure phase. The body residue of CP decreased once it reached a peak level during the early stage of exposure, indicating that the initial uptake of CP rapidly induced biotransformation with the synthesis of new CYP metabolic proteins. The residual chlorpyrifos-oxon concentration, an acetylcholinesterase (AChE) inhibitor, continuously increased even after the recovery regime started. These delayed toxicokinetics seem to be important for the extension of AChE inhibition for up to 9 h after the start of the recovery regime. Comprehensive investigation into the molecular initiation events and changes in the internal concentrations of chemical species provide insight into response causality within the framework of an adverse outcome pathway.
由于化学物质从环境中被吸收，暴露于化学物质的生物体内部的化学物质浓度会随时间而变化，这些过程包括吸收、分布、代谢和排泄。当使用生物标志物来评估环境污染物的潜在危害和风险时，内部浓度和时间是毒性的重要修饰物。在本研究中，全面研究了分子生物标志物的反应以及化学物质在体内的命运，以确定随时间推移的因果关系。选择毒死蜱（CP）作为模型化学物质，采用被动给药方法将秀丽隐杆线虫暴露于 CP 中 4 小时。然后，在 48 小时的恢复阶段，在新鲜培养基中监测蠕虫。在持续暴露阶段，与 CYP 代谢相关的基因（cyp35a2 和 cyp35a3）的 mRNA 表达增加。一旦 CP 在暴露早期达到峰值水平，体内 CP 的残留量就会减少，这表明 CP 的初始吸收迅速诱导了生物转化，合成了新的 CYP 代谢蛋白。残留的毒死蜱氧（一种乙酰胆碱酯酶（AChE）抑制剂）的浓度在恢复阶段开始后仍持续增加。这些延迟的毒代动力学似乎对恢复阶段开始后长达 9 小时的 AChE 抑制的延长很重要。对分子起始事件和化学物质内部浓度变化的综合研究，为在不良结局途径框架内深入了解反应因果关系提供了依据。
