Hexavalent chromium and cellular senescence: A comprehensive analysis from chromate-exposed occupational population and chromate-inhaled mouse model

作者：Zhiqiang Ji, Yali Zhang, Guiping Hu, Shiyi Hong, Zekang Su, Qiaojian Zhang, Li Wang, Tiancheng Wang, Shanfa Yu, Qian Bu, Fang Yuan, Xiaojun Zhu, Guang Jia · 发表于：Journal of Hazardous Materials · 年份：2025 · DOI：10.1016/j.jhazmat.2025.138387 · 被引用次数：6 · 研究领域：Hydrogen's biological and therapeutic effects、Heavy Metal Exposure and Toxicity、Chromium effects and bioremediation

Cellular senescence may predominantly drive the progression of early subclinical injury under conditions of low-dose, long-term occupational exposure. However, previous research has largely overlooked the cellular senescence induced by hexavalent chromium [Cr(VI)]. To bridge the gap, 304 workers from a chromate facility were enrolled, and a mouse model was used to confirm the effects of Cr(VI) on cellular senescence. A 2.7-fold increase in blood Cr was related to the changes of p53 [23.19 (13.06, 34.23)%], serum α-Klotho [11.45 (6.13, 17.04)%], adipsin [-14.11(-22.16, -5.24)%], leptin [-4.32(-6.99, -1.58)%] and resistin [-3.29(-5.54, -0.98)%]. There were significant correlations of blood Cr with DNA methylation of ELOVL2 and hTERT genes. Furthermore, methylation at hTERT Pos1, Pos2, Pos6, and Pos8 significantly mediated the relationship between blood Cr and p53. In the mouse model, we observed significantly higher mRNA expression levels of key genes in the p53/p21 and Rb/p16 pathways and senescence-associated β-galactosidase positive cell ratio in the exposed group. In conclusion, we found that p53 in human peripheral blood cells serves as a Cr(VI)-induced senescence biomarker, with α-Klotho upregulation and adipokines (adipsin, leptin, and resistin) downregulation indicating compensatory responses, as well as hTERT methylation partially mediating Cr(VI)-senescence association.