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

Jiayu Xu; Qiaojian Zhang; Zekang Su; Yu Liu; Tenglong Yan; Yali Zhang; Tiancheng Wang; Xuetao Wei; Zhangjian Chen; Guiping Hu; Tian Chen; Guang Jia

doi:10.1016/j.envint.2022.107636

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

Environ Int. 2022 Dec:170:107636. doi: 10.1016/j.envint.2022.107636. Epub 2022 Nov 19.

Authors

Jiayu Xu¹, Qiaojian Zhang¹, Zekang Su¹, Yu Liu¹, Tenglong Yan¹, Yali Zhang¹, Tiancheng Wang², Xuetao Wei³, Zhangjian Chen¹, Guiping Hu⁴, Tian Chen⁵, Guang Jia⁶

Affiliations

¹ Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100083, China.
² Department of Clinical Laboratory, Third Hospital of Peking University, Beijing 100083, China.
³ Department of Toxicology, School of Public Health, Peking University, Beijing 100083, China.
⁴ School of Medical Science and Engineering, Beihang University, Beijing 100191, China.
⁵ School of Public Health and Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
⁶ Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100083, China. Electronic address: jiaguangjia@bjmu.edu.cn.

PMID: 36423397
DOI: 10.1016/j.envint.2022.107636

Abstract

Ambient air pollution was classified as carcinogenic to humans (Group 1) for lung cancer. DNA damage was an important first step in the process of carcinogenesis, and could also be induced by air pollution. In this study, intratracheal instillation and real-time air exposure system were combined to establish SHP (short-term high-level PM_2.5) and LLPO (long-term low-level PM_2.5 and O₃) exposure patterns, respectively. Hierarchical levels of genetic biomarkers were analyzed to explore DNA damage effects in rats. Representative DNA repair genes from different repair pathways were selected to explore the relative expression levels. The methylation level of differentially expressed repair genes were also determined. Besides, miRNA sequencing and non-targeted metabolomic analysis were performed in rat lungs. KEGG and multi-omics analysis were used to explore the potential mechanism of genetic damage under different air pollution patterns. We found that LLPO exposure induced DSBs and chromosome damage. SHP exposure could induce DSBs and DNA oxidative damage, and the effects of genetic damage under this pollution pattern could be repaired by natural repair. Repair genes involved in two pattern were different. SHP exposure could induce higher methylation levels of RAD51, which might be a potential epigenetic mechanism for high-level PM_2.5 induced down-regulated expression of RAD51 and DSBs. Besides, 29 overlapped alterations in metabolic pathways were identified by metabolomic and miRNA sequencing, including purine metabolism and pyrimidine metabolism after LLPO exposure. Differential miRNAs expression in lung tissue were associated with apoptosis, DNA damage and damage repair. We concluded that under different air pollution patterns, DNA damage biomarkers and activated targets of DNA damage repair network were both different. The genetic damage effects caused by high-level short-term PM_2.5 can be alleviated by natural repair. We provided possible mechanisms by multi-omics which could explain the increased carcinogenic risk caused by air pollution.

Keywords: Air pollution; Genetic damage; Metabolomics; Methylation; MiRNA.

MeSH terms

Air Pollution*
Animals
Carcinogenesis*
DNA Breaks, Double-Stranded*
DNA Repair Enzymes* / genetics
Environmental Exposure*
Humans
Lung
Metabolomics
MicroRNAs* / genetics
Multiomics
Particulate Matter*
Rats

Substances

MicroRNAs
DNA Repair Enzymes
Particulate Matter