Targeted methods that dominated toxicological research until recently did not allow for screening of all molecular changes involved in toxic response. Therefore, it is difficult to infer if all major mechanisms of toxicity have already been discovered, or if some of them are still overlooked. We used data on 591,084 unique chemical-gene interactions to identify genes and molecular pathways most sensitive to chemical exposures. The list of identified pathways did not change significantly when analyses were done on different subsets of data with non-overlapping lists of chemical compounds indicative that our dataset is saturated enough to provide unbiased results. One of the most important findings of this study is that almost every known molecular mechanism may be affected by chemical exposures. Predictably, xenobiotic metabolism pathways, and mechanisms of cellular response to stress and damage were among the most sensitive. Additionally, we identified highly sensitive molecular pathways, which are not widely recognized as major targets of toxicants, including lipid metabolism pathways, longevity regulation cascade, and cytokine-mediated signaling. These mechanisms are relevant to significant public health problems, such as aging, cancer, metabolic and autoimmune disease. Thus, public health field will benefit from future focus of toxicological research on identified sensitive mechanisms.

直到最近，在毒理学研究中占主导地位的有针对性的方法还不能筛选涉及毒性反应的所有分子变化。因此，很难推断出是否已经发现了所有主要的毒性机理，或者是否仍忽略了其中一些。我们使用了591,084种独特的化学-基因相互作用的数据来鉴定对化学暴露最敏感的基因和分子途径。当对不同子集的数据进行分析时，发现的途径列表没有明显变化，其中不重叠的化合物列表表明我们的数据集已经足够饱和，可以提供无偏见的结果。这项研究最重要的发现之一是，几乎每个已知的分子机制都可能受到化学暴露的影响。可以预见的是，异源代谢途径 细胞对压力和损伤的反应机制是最敏感的。此外，我们确定了高度敏感的分子途径，这些途径未被广泛认为是有毒物质的主要靶标，包括脂质代谢途径，寿命调节级联和细胞因子介导的信号传导。这些机制与重大的公共健康问题有关，例如衰老，癌症，代谢和自身免疫性疾病。因此，公共卫生领域将受益于毒理学研究对确定的敏感机制的未来关注。和细胞因子介导的信号传导。这些机制与重大的公共健康问题有关，例如衰老，癌症，代谢和自身免疫性疾病。因此，公共卫生领域将受益于毒理学研究对确定的敏感机制的未来关注。和细胞因子介导的信号传导。这些机制与重大的公共健康问题有关，例如衰老，癌症，代谢和自身免疫性疾病。因此，公共卫生领域将受益于毒理学研究对确定的敏感机制的未来关注。