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

SIMPLE SUMMARY: A cesium-bearing microparticle (Cs-BMP) is an insoluble radioactive microparticle possessing high specific radioactivity, which was discovered after the incident at the Fukushima nuclear power plant. Due to their insoluble nature, such Cs-BMPs are assumed to adhere in the long term to normal tissue, leading to chronic local exposure. However, radiation risk due to the intake of internal exposure to radioactive cesium is conventionally estimated from the organ dose given by uniform exposure to soluble cesium. As such, it is critical to clarify the normal tissue effects posed by heterogeneous exposure to Cs-BMPs. This in vitro study reports on the relationship between the inflammatory responses and DNA damage induction during local exposure to a Cs-BMP. ABSTRACT: 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 (137)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.