Inflammation response, oxidative stress and DNA damage caused by urban air pollution exposure increase in the lack of DNA repair XPC protein

Author(s):Show less -

Alves, Nilmara de Oliveira ^[1] ; Pereira, Guilherme Martins ^[2] ; Di Domenico, Marlise ^[1] ; Costanzo, Giovanna ^[1] ; Benevenuto, Sarah ^[3] ; Fonoff, Adriana M. de Oliveira ^[1] ; Xavier Costa, Natalia de Souza ^[1] ; Ribeiro, Jr., Gabriel ^[1] ; Kajitani, Gustavo Satoru ^[4] ; Moreno, Natalia Cestari ^[4] ; Fotoran, Wesley ^[4] ; Torres, Janaina Iannicelli ^[1] ; de Andrade, Jailson Bittencourt ^[5] ; Veras, Mariana Matera ^[1] ; Artaxo, Paulo ^[6] ; Martins Menck, Carlos Frederico ^[4] ; Vasconcellos, Perola de Castro ^[2] ; Saldiva, Paulo ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Chem Inst, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Vet Med & Anim Sci, Dept Surg, Sect Anat, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[5] SENAI CIMATEC Univ Ctr, Salvador, BA - Brazil

^[6] Univ Sao Paulo, Inst Phys, Sao Paulo - Brazil

• Document type: Journal article
• Source: Environment International; v. 145, DEC 2020.
• Web of Science Citations: 0

Abstract

Air pollution represents a considerable threat to health worldwide. The Sao Paulo Metropolitan area, in Brazil, has a unique composition of atmospheric pollutants with a population of nearly 20 million people and 9 million passenger cars. It is long known that exposure to particulate matter less than 2.5 mu m (PM2.5) can cause various health effects such as DNA damage. One of the most versatile defense mechanisms against the accumulation of DNA damage is the nucleotide excision repair (NER), which includes XPC protein. However, the mechanisms by which NER protects against adverse health effects related to air pollution are largely unknown. We hypothesized that reduction of XPC activity may contribute to inflammation response, oxidative stress and DNA damage after PM2.5 exposure. To address these important questions, XPC knockout and wild type mice were exposed to PM2.5 using the Harvard Ambient Particle concentrator. Results from one-single exposure have shown a significant increase in the levels of anti-ICAM, IL-1 beta, and TNF-alpha in the polluted group when compared to the filtered air group. Continued chronic PM2.5 exposure increased levels of carbonylated proteins, especially in the lung of XPC mice, probably as a consequence of oxidative stress. As a response to DNA damage, XPC mice lungs exhibit increased gamma-H2AX, followed by severe atypical hyperplasia. Emissions from vehicles are composed of hazardous substances, with polycyclic aromatic hydrocarbons (PAHs) and metals being most frequently cited as the major contributors to negative health impacts. This analysis showed that benzo{[}b]fluoranthene, 2-nitrofluorene and 9,10-anthraquinone were the most abundant PAHs and derivatives. Taken together, these findings demonstrate the participation of XPC protein, and NER pathway, in the protection of mice against the carcinogenic potential of air pollution. This implicates that DNA is damaged directly (forming adducts) or indirectly (Reactive Oxygen Species) by the various compounds detected in urban PM2.5. (AU)

• FAPESP's process: 17/17047-0 - Aerosol and clouds life cycles in Amazonia: biogenic emissions, biomass burning and impacts on ecosystem
• Grantee: Paulo Eduardo Artaxo Netto
• Support Opportunities: Research Program on Global Climate Change - Thematic Grants
• FAPESP's process: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg)
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/21728-2 - The use of modern autopsy techniques to investigate human diseases (MODAU)
• Grantee: Paulo Hilário Nascimento Saldiva
• Support Opportunities: Research Projects - Thematic Grants