Genetic damage and potential mechanism exploration under different air pollution patterns by multi-omics

Area of Science:

• Environmental Health
• Toxicology
• Molecular Biology
• Genetics

Background:

• Ambient air pollution is a Group 1 carcinogen, increasing lung cancer risk.
• DNA damage is a critical early step in carcinogenesis, and air pollutants can induce it.
• Understanding the specific genetic damage and repair mechanisms is crucial for risk assessment.

Purpose of the Study:

• To investigate DNA damage and repair responses in rats exposed to distinct air pollution patterns.
• To explore potential epigenetic and metabolic mechanisms underlying air pollution-induced genetic damage.
• To elucidate the differences in genetic damage and repair pathways under short-term high-level vs. long-term low-level exposure.

Main Methods:

• Established short-term high-level (SHP) and long-term low-level (LLPO) particulate matter (PM2.5) and ozone (O3) exposure models in rats.
• Analyzed genetic biomarkers, including DNA repair gene expression and methylation levels.
• Performed miRNA sequencing and non-targeted metabolomic analysis, followed by multi-omics and KEGG pathway analysis.

Main Results:

• LLPO exposure induced double-strand breaks (DSBs) and chromosome damage.
• SHP exposure induced DSBs and oxidative DNA damage, which were mitigated by natural repair mechanisms.
• Distinct DNA repair genes were activated under SHP and LLPO conditions; SHP exposure increased RAD51 methylation, potentially down-regulating its expression.

Conclusions:

• Different air pollution patterns trigger distinct DNA damage biomarkers and activate specific DNA repair pathways.
• Genetic damage from short-term high-level PM2.5 exposure can be alleviated by natural repair.
• Multi-omics analysis provides insights into mechanisms linking air pollution exposure to increased carcinogenic risk.