Department of Pathology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
Chemistry Institute, University of Sao Paulo, Sao Paulo, Brazil.
Environ Int. 2020 Dec;145:106150. doi: 10.1016/j.envint.2020.106150. Epub 2020 Oct 8.
Air pollution represents a considerable threat to health worldwide. The São 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 µm (PM) 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 PM exposure. To address these important questions, XPC knockout and wild type mice were exposed to PM using the Harvard Ambient Particle concentrator. Results from one-single exposure have shown a significant increase in the levels of anti-ICAM, IL-1β, and TNF-α in the polluted group when compared to the filtered air group. Continued chronic PM 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 γ-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 PM.
空气污染对全球健康构成了重大威胁。巴西圣保罗大都市区的大气污染物成分独特，拥有近 2000 万人口和 900 万辆汽车。众所周知，暴露于小于 2.5 µm（PM）的颗粒物会导致各种健康影响，如 DNA 损伤。核苷酸切除修复（NER）是一种最通用的防御机制，可以修复 DNA 损伤，其中包括 XPC 蛋白。然而，NER 如何保护人体免受与空气污染相关的不良健康影响在很大程度上尚不清楚。我们假设 XPC 活性的降低可能导致 PM 暴露后炎症反应、氧化应激和 DNA 损伤。为了解决这些重要问题，我们使用哈佛环境粒子浓缩器使 XPC 敲除和野生型小鼠暴露于 PM 中。单次暴露的结果表明，与过滤空气组相比，污染组中抗细胞间黏附分子（ICAM）、白细胞介素 1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的水平显著增加。持续的慢性 PM 暴露增加了羰基化蛋白的水平，尤其是在 XPC 小鼠的肺部，这可能是氧化应激的结果。作为对 DNA 损伤的反应，XPC 小鼠的肺部表现出增加的 γ-H2AX，随后出现严重的非典型增生。车辆排放物由有害物质组成，多环芳烃（PAHs）和金属最常被认为是对健康产生负面影响的主要因素。该分析表明，苯并[b]荧蒽、2-硝基芴和 9,10-蒽醌是最丰富的 PAHs 和衍生物。综上所述，这些发现表明 XPC 蛋白和 NER 途径参与了保护小鼠免受空气污染致癌潜力的侵害。这表明 DNA 直接（形成加合物）或间接（活性氧物质）受到城市 PM 中检测到的各种化合物的损伤。
