Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: atrazine

Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to atrazine (AZ). For AZ, the physiological mode of action predicted by DEBtox was increased cost for maintenance. The transcriptional analysis demonstrated that this increase resulted from effects on DNA integrity as indicated by changes in the expression of genes chromosomal repair. Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes.本研究以秀丽隐杆线虫（Caenorhabditis elegans）为实验材料，采用DEBtox（毒理学动态能量预算模型，dynamic energy budget in toxicology）生理建模方法结合转录谱分析，旨在明确莠去津（atrazine，AZ）暴露后，以系统级资源分配效应为表征的生理作用模式与基因表达变化之间的关联。针对莠去津，DEBtox模型预测其生理作用模式为机体维持成本升高。转录组分析结果显示，该维持成本升高源于对DNA完整性的影响，具体体现为染色体修复相关基因的表达变化。本研究结果证实，基于过程的模型输出与转录组学分析结果可用于关联有毒化学物质的作用机制与后续的群体效应。此类互补分析方法可为风险评估中的化学品分类工作提供辅助支持。