D'Agostini Francesco, La Maestra Sebastiano
Department of Health Sciences (DISSAL), Section of Hygiene and Preventive Medicine, University of Genoa, Via A. Pastore, 1, 16132, Genoa, Italy.
Arch Toxicol. 2025 Jan;99(1):211-224. doi: 10.1007/s00204-024-03894-0. Epub 2024 Oct 25.
DNA damage is one of the primary mechanisms underlying cancer and other chronic degenerative diseases. Early evaluation of this damage in the affected cells and tissues is crucial for understanding pathogenesis and implementing effective prevention strategies. However, isolating target cells from affected organs, such as the lungs, can be challenging. Therefore, an alternative approach is to evaluate genotoxic damage in surrogate cells. Pulmonary alveolar macrophages are ideally suited for this purpose because they are in close contact with the target cells of the bronchial and alveolar epithelium, share the exact mechanisms and levels of exposure, and are easily recoverable in large numbers. This review comprehensively lists all studies using alveolar macrophages as surrogate cells to show genotoxic lung damage in humans or laboratory animals. These investigations provide fundamental information on the mechanisms of DNA damage in the lung and allow for better assessment and management of risk following exposure to inhalable genotoxic agents. Furthermore, they may be a valuable tool in cancer chemoprevention, helping the right choice of agents for clinical trials.
DNA损伤是癌症和其他慢性退行性疾病的主要潜在机制之一。对受影响细胞和组织中的这种损伤进行早期评估对于理解发病机制和实施有效的预防策略至关重要。然而，从受影响的器官（如肺）中分离靶细胞可能具有挑战性。因此，一种替代方法是评估替代细胞中的基因毒性损伤。肺泡巨噬细胞非常适合此目的，因为它们与支气管和肺泡上皮的靶细胞密切接触，具有相同的暴露机制和水平，并且易于大量回收。本综述全面列出了所有使用肺泡巨噬细胞作为替代细胞来显示人类或实验动物基因毒性肺损伤的研究。这些研究提供了关于肺中DNA损伤机制的基本信息，并有助于更好地评估和管理接触可吸入基因毒性剂后的风险。此外，它们可能是癌症化学预防中的一种有价值的工具，有助于为临床试验正确选择药物。
