Cellular senescence mediates hexavalent chromium-associated lung function decline: Insights from a structural...

Area of Science:

• Environmental Health
• Occupational Medicine
• Toxicology

Background:

• Hexavalent chromium [Cr(VI)] exposure is linked to lung function decline and disease.
• Mechanisms involving systemic inflammation, oxidative stress, and cellular senescence remain underexplored.
• Simultaneous investigation of these pathways is crucial for understanding Cr(VI) toxicity.

Purpose of the Study:

• To investigate the mechanisms of Cr(VI)-induced lung function decline.
• To explore the roles of oxidative stress and cellular senescence in chromate production workers.
• To identify novel biomarkers for Cr(VI) exposure.

Main Methods:

• Cross-sectional study of 304 Chinese chromate production workers.
• Analysis of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α).
• Detection of mRNA, telomere length, and ribosomal DNA copy numbers (rDNA CNs) in peripheral blood cells.
• Structural equation modeling to assess mediation effects.

Main Results:

• Elevated blood chromate correlated with increased urinary 8-OHdG and 8-iso-PGF2α, indicating oxidative stress.
• Blood chromate levels showed strong correlations with mRNA levels in the cellular senescence pathway (P16, P21, TP53, P15).
• Chromate exposure was associated with decreased telomere length and altered rDNA CNs.
• Cellular senescence mediated 23.3% of the Cr(VI)-associated lung function decline.

Conclusions:

• Urinary 8-iso-PGF2α, telomere length, and rDNA CNs show promise as novel biomarkers of chromate exposure.
• Cellular senescence plays a significant role in the mechanisms underlying Cr(VI)-induced lung function impairment.
• Findings underscore the importance of managing Cr(VI) exposure to prevent occupational lung disease.