POLE 缺陷加剧柴油发动机排气引起的基因组不稳定性和支气管上皮细胞恶性转变
Pimei Zhang1,2, Zhaoxu Wu1,2, Qiang Ju1,2
1Department of Blood Transfusion, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, Shandong, 266000, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|June 30, 2025
概括
柴油发动机排气暴露导致小鼠肺状细胞癌,诱导DNA损伤和基因组不稳定性,特别是当聚合酶epsilon (POLE) 功能不足时. 这突显了癌症发展中的基因环境相互作用.
科学领域:
- 环境健康 环境健康
- 分子生物学分子生物学
- 致癌的发生是致癌的产生.
背景情况:
- 柴油发动机废气 (DEE) 是已知的致癌物质,但直接的实验证据将其与癌症诱导联系起来是有限的.
- 了解DEE诱导致癌的分子机制对于公共卫生至关重要.
研究的目的:
- 提供DEE诱导致癌的直接实验证据.
- 阐明分子机制,包括基因突变和途径改变,是DEE诱导的肺癌的基础.
主要方法:
- 支气管上皮细胞暴露于DEE以及随后的体外和体内瘤生成试验.
- 全基因组测序和RNA测序用于识别突变特征,拷贝数变异和差异表达基因.
- 测试以确认DNA修复途径的缺陷,如聚合酶epsilon (POLE) 和不匹配修复 (MMR).
主要成果:
- 在免疫缺陷小鼠中,DEE暴露诱导了肺状细胞癌.
- 确定了与POLE和MMR缺陷相关的DEE诱导的突变特征 (DBS3,ID1/ID2).
- 在转化细胞中观察到抑制DNA损伤修复和激活与癌症相关的信号通路 (JAK-STAT,PI3K-Akt,MAPK).
结论:
- 通过诱导基因组不稳定性和高突变负担,DEE暴露可以直接导致肺癌.
- 波尔缺陷加剧了DEE诱导的DNA损伤和恶性转变,强调了癌症发生过程中的基因环境相互作用.
相关概念视频
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
3.1K
Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Chronic Inflammation
3.1K
01:20Chronic Obstructive Pulmonary Disease-I: Introduction
2.9K
Chronic Obstructive Pulmonary Disease (COPD) is a long-lasting respiratory condition requiring continuous attention and care. It is a progressive lung disease that leads to breathing challenges due to airflow obstruction. It manifests as persistent respiratory symptoms and restricted airflow resulting from abnormalities in the airways and alveoli, usually due to long-term exposure to harmful particles or gases. COPD mainly consists of two primary conditions: emphysema and chronic bronchitis.
2.9K
01:22Chronic Obstructive Pulmonary Disease
1.4K
COPD is defined as a heterogeneous lung condition marked by persistent respiratory symptoms such as dyspnea, cough, and sputum production, caused by abnormalities in the airways that cause airflow obstruction.
Smoking is a primary risk factor for COPD, with over 80% of patients having a history of it. Patients typically experience progressive dyspnea or labored breathing, frequent coughing, and recurrent pulmonary infections. Many eventually succumb to respiratory failure, characterized by...
Smoking is a primary risk factor for COPD, with over 80% of patients having a history of it. Patients typically experience progressive dyspnea or labored breathing, frequent coughing, and recurrent pulmonary infections. Many eventually succumb to respiratory failure, characterized by...
1.4K
01:25Chronic Obstructive Pulmonary Disease-III: Symptoms and Complications.
2.9K
Understanding the variety of primary symptoms and systemic complications that characterize chronic obstructive pulmonary disease (COPD) is crucial for healthcare professionals.
Symptoms of COPD can be classified as primary or systemic. Primary symptoms relate to reduced airflow, while systemic or extrapulmonary symptoms relate to COPD's broader impact on the body.
Primary Symptoms of COPD:
Symptoms of COPD can be classified as primary or systemic. Primary symptoms relate to reduced airflow, while systemic or extrapulmonary symptoms relate to COPD's broader impact on the body.
Primary Symptoms of COPD:
2.9K
01:20COPD: Pathogenesis and Clinical Features
535
Chronic obstructive pulmonary disease (COPD) is a group of lung conditions that progressively worsen over time, including chronic bronchitis and emphysema. This cluster of diseases collectively leads to a gradual and irreversible decline in lung function over time.
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
535
01:17Other Pulmonary Disorders
914
Respiratory disorders encompass a range of conditions with varying levels of severity. Asthma, marked by chronic airway inflammation and hypersensitivity, is one such condition. It can lead to airway obstruction due to factors like bronchial spasms, mucosal edema, increased mucus secretion, or epithelial damage. Asthma triggers are diverse, ranging from allergens to emotional upset, and treatment focuses on both immediate relief through bronchodilators and long-term inflammation suppression.
914