Zhang Jing, Koch Iris, Gibson Laura A, Loughery Jennifer R, Martyniuk Christopher J, Button Mark, Caumette Guilhem, Reimer Kenneth J, Cullen William R, Langlois Valerie S
*Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, ON, Canada, K7K 7B4;
University of New Brunswick and Canadian River Institute, NB, Canada, E2L 4L5;
Toxicol Sci. 2015 Dec;148(2):603-17. doi: 10.1093/toxsci/kfv207. Epub 2015 Oct 1.
Arsenic compounds are widespread environmental contaminants and exposure elicits serious health issues, including early developmental anomalies. Depending on the oxidation state, the intermediates of arsenic metabolism interfere with a range of subcellular events, but the fundamental molecular events that lead to speciation-dependent arsenic toxicity are not fully elucidated. This study therefore assesses the impact of arsenic exposure on early development by measuring speciation and gene expression profiles in the developing Western clawed frog (Silurana tropicalis) larvae following the environmental relevant 0.5 and 1 ppm arsenate exposure. Using HPLC-ICP-MS, arsenate, dimethylarsenic acid, arsenobetaine, arsenocholine, and tetramethylarsonium ion were detected. Microarray and pathway analyses were utilized to characterize the comprehensive transcriptomic responses to arsenic exposure. Clustering analysis of expression data showed distinct gene expression patterns in arsenate treated groups when compared with the control. Pathway enrichment revealed common biological themes enriched in both treatments, including cell signal transduction, cell survival, and developmental pathways. Moreover, the 0.5 ppm exposure led to the enrichment of pathways and biological processes involved in arsenic intake or efflux, as well as histone remodeling. These compensatory responses are hypothesized to be responsible for maintaining an in-body arsenic level comparable to control animals. With no appreciable changes observed in malformation and mortality between control and exposed larvae, this is the first study to suggest that the underlying transcriptomic regulations related to signal transduction, cell survival, developmental pathways, and histone remodeling may contribute to maintaining ongoing development while coping with the potential arsenic toxicity in S. tropicalis during early development.
砷化合物是广泛存在的环境污染物，接触砷会引发严重的健康问题，包括早期发育异常。根据氧化态的不同，砷代谢的中间产物会干扰一系列亚细胞事件，但导致特定形态砷毒性的基本分子事件尚未完全阐明。因此，本研究通过测量环境相关浓度0.5和1 ppm砷酸盐暴露后发育中的西方爪蟾（热带爪蟾）幼体的形态和基因表达谱，评估砷暴露对早期发育的影响。使用高效液相色谱-电感耦合等离子体质谱法，检测到了砷酸盐、二甲基砷酸、砷甜菜碱、砷胆碱和四甲基砷离子。利用微阵列和通路分析来表征对砷暴露的全面转录组反应。与对照组相比，表达数据的聚类分析显示砷酸盐处理组有明显不同的基因表达模式。通路富集揭示了两种处理中共同富集的生物学主题，包括细胞信号转导、细胞存活和发育通路。此外，0.5 ppm的暴露导致参与砷摄入或流出以及组蛋白重塑的通路和生物学过程的富集。据推测，这些补偿性反应负责维持与对照动物相当的体内砷水平。在对照幼体和暴露幼体之间未观察到畸形和死亡率有明显变化，这是第一项表明与信号转导、细胞存活、发育通路和组蛋白重塑相关的潜在转录组调控可能有助于在热带爪蟾早期发育过程中应对潜在砷毒性的同时维持发育进程的研究。
