Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences & Medicine, Department of Medical and Molecular Genetics, Guy's Hospital, London, SE1 9RT, UK.
Toxys, De Limes 7, 2342, DH, Oegstgeest, the Netherlands.
Food Chem Toxicol. 2021 Nov;157:112601. doi: 10.1016/j.fct.2021.112601. Epub 2021 Oct 6.
The current generation of carcinogenicity tests is often insufficient to predict cancer outcomes from pesticide exposures. In order to facilitate health risk assessment, The International Agency for Research on Cancer identified 10 key characteristics which are commonly exhibited by human carcinogens. The ToxTracker panel of six validated GFP-based mouse embryonic stem reporter cell lines is designed to measure a number of these carcinogenic properties namely DNA damage, oxidative stress and the unfolded protein response. Here we present an evaluation of the carcinogenic potential of the herbicides glyphosate, 2,4-D and dicamba either alone or in combination, using the ToxTracker assay system. The pesticide 2,4-D was found to be a strong inducer of oxidative stress and an unfolded protein response. Dicamba induced a mild oxidative stress response, whilst glyphosate did not elicit a positive outcome in any of the assays. The results from a mixture of the three herbicides was primarily an oxidative stress response, which was most likely due to 2,4-D with dicamba or glyphosate only playing a minor role. These findings provide initial information regarding the risk assessment of carcinogenic effects arising from exposure to a mixture of these herbicides.
当前一代的致癌性测试往往不足以预测农药暴露引起的癌症结果。为了促进健康风险评估，国际癌症研究机构确定了 10 个常见的人类致癌物的特征。ToxTracker 面板由 6 种经过验证的基于 GFP 的小鼠胚胎干细胞报告细胞系组成，旨在测量许多致癌特性，即 DNA 损伤、氧化应激和未折叠蛋白反应。在这里，我们使用 ToxTracker 测定系统评估了除草剂草甘膦、2,4-D 和麦草畏单独或联合使用的致癌潜力。研究发现，2,4-D 是一种强烈的氧化应激和未折叠蛋白反应诱导剂。麦草畏诱导轻度氧化应激反应，而草甘膦在任何测定中均未产生阳性结果。三种除草剂的混合物的结果主要是氧化应激反应，这主要是由于 2,4-D，而麦草畏或草甘膦仅起次要作用。这些发现提供了有关接触这些除草剂混合物引起致癌作用的风险评估的初步信息。
