Inflammatory Signaling and DNA Damage Responses after Local Exposure to an Insoluble Radioactive Microparticle

• Published in: Cancers 2022-02, Vol.14 (4), p.1045
• Main Authors: Matsuya, Yusuke, Hamada, Nobuyuki, Yachi, Yoshie, Satou, Yukihiko, Ishikawa, Masayori, Date, Hiroyuki, Sato, Tatsuhiko
• Format: Article
• Language: English
• Subjects: Cell culture; Cell lines; Cesium; Cyclooxygenase-2; Cytokines; Deoxyribonucleic acid; DNA; DNA damage; Epithelial cells; Histone H2A; Inflammation; Inhalation; Microparticles; NF-κB protein; Nuclear power plants; Radiation; Radioactivity; Radiosensitivity; Respiratory system; Spatial distribution; Transcription factors; Tumor necrosis factor-TNF
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14041045

Cesium-bearing microparticles (Cs-BMPs) can reach the human respiratory system after inhalation, resulting in chronic local internal exposure. We previously investigated the spatial distribution of DNA damage induced in areas around a Cs-BMP; however, the biological impacts have not been fully clarified due to the limited amount of data. Here, we investigated the inflammatory signaling and DNA damage responses after local exposure to a Cs-BMP in vitro. We used two normal human lung cell lines, i.e., lung fibroblast cells (WI-38) and bronchial epithelial cells (HBEC3-KT). After 24 h exposure to a Cs-BMP, inflammation was evaluated by immunofluorescent staining for nuclear factor κB (NF-κB) p65 and cyclooxygenase 2 (COX-2). The number of DNA double-strand breaks (DSBs) was also detected by means of phospholylated histone H2AX (γ-H2AX) focus formation assay. Cs-BMP exposure significantly increased NF-κB p65 and COX-2 expressions, which were related to the number of γ-H2AX foci in the cell nuclei. Compared to the uniform (external) exposure to Cs γ-rays, NF-κB tended to be more activated in the cells proximal to the Cs-BMP, while both NF-κB p65 and COX-2 were significantly activated in the distal cells. Experiments with chemical inhibitors for NF-κB p65 and COX-2 suggested the involvement of such inflammatory responses both in the reduced radiosensitivity of the cells proximal to Cs-BMP and the enhanced radiosensitivity of the cells distal from Cs-BMP. The data show that local exposure to Cs-BMP leads to biological effects modified by the NF-κB pathway, suggesting that the radiation risk for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.