Cellular senescence mediates hexavalent chromium-associated lung function decline: Insights from a structural equation Model,Environmental Pollution

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Cellular senescence mediates hexavalent chromium-associated lung function decline: Insights from a structural equation Model
Environmental Pollution ( IF 8.9 ) Pub Date : 2024-04-10 , DOI: 10.1016/j.envpol.2024.123947
Yali Zhang , Guiping Hu , Qiaojian Zhang , Shiyi Hong , Zekang Su , Li Wang , Tiancheng Wang , Shanfa Yu , Fang Yuan , Xiaojun Zhu , Guang Jia

There is sufficient evidence suggesting that exposure to hexavalent chromium [Cr(VI)] can cause a decline in lung function and the onset of lung diseases. However, no studies have yet explored the underlying mechanisms of these effects from various perspectives such as systemic inflammation, oxidative stress, and cellular senescence, simultaneously. This cross-sectional study was conducted among 304 workers engaged in chromate production and processing in China. Urine was used for detection of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α), while RNA and DNA extraction from peripheral blood cells was used for detection of mRNA, telomere length, and ribosomal DNA copy numbers (rDNA CNs). A 2.7-fold elevation in blood chromate (Cr) corresponded to a 7.86% (95% CI: 2.57%, 13.42%) rise in urinary 8-OHdG and a 4.14% (0.02%, 8.42%) increase in urinary 8-iso-PGF2α, indicating that exposure to chromates can cause oxidative stress. Furthermore, strong correlations emerged between blood Cr concentration and mRNA levels of P16, P21, TP53, and P15 in the cellular senescence pathway. Simultaneously, a 2.7-fold elevation in blood Cr associated with a −5.47% (−8.72%, −2.1%) change in telomere length, while rDNA CNs (5S, 5.8S, 18S, and 28S) changed by −3.91% (−7.99%, 0.34%), −9.4% (−15.73%, −2.6%), −8.06% (−14.01%, −1.69%), and −5.86% (−10.67%, −0.78%), respectively. Structural equation model highlighted that cellular senescence exerted significant indirect effects on Cr(VI)-associated lung function decline, with a mediation proportion of 23.3%. This study provided data supporting for 8-iso-PGF2α, telomere length, and rDNA CNs as novel biomarkers of chromate exposure, emphasizing the significant role of cellular senescence in the mechanism underlying chromate-induced lung function decline.

更新日期：2024-04-10

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