Inflammatory signaling and DNA damage responses after local exposure to an insoluble radioactive microparticle

Matsuya, Yusuke  ; Hamada, Nobuyuki*; Yachi, Yoshie*; Satou, Yukihiko   ; Ishikawa, Masayori*; Date, Hiroyuki*; Sato, Tatsuhiko   

An insoluble cesium-bearing microparticle (Cs-BMP) was discovered after the incident at the Fukushima nuclear power plant. Radiation risk by intake of internal exposure to radioactive cesium is conventionally estimated from organ dose, assuming that soluble cesium is uniformly distributed throughout human body. Meanwhile, such Cs-BMPs are assumed to adhere in the long term to normal tissue, leading to chronic non-uniform exposure. In this study, to clarify the normal tissue effects for Cs-BMP exposure, we investigated the relationship between the inflammatory responses and DNA damage induction. From experiments focusing on the inflammatory signaling pathways such as NF-B p65 and COX-2, compared to the uniform exposure to -rays, NF-B p65 tended to be more activated in the cells proximal to the Cs-BMP, while both NF-B p65 and COX-2 were significantly activated in the distal cells. Experiments with inhibitors for NF-B p65 and COX-2 suggested 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. These results suggested that radiation effects for Cs-BMP exposure can differ from that estimated based on conventional uniform exposure to normal tissues.