マイクロビーム誘発細胞質損傷を起因とした防御的な細胞応答の解析

Primary target of radiation is the cellular DNA, but consequence of cytoplasmic damage is yet to be understood. Taking advantage of SPICE-QST microbeam, we performed a cytoplasm targeted irradiation (Cyto-IR) of the WI-38  cells to investigate the cytoplasmic damage response. We focused on the activation of nuclear factor (erythroid-derived 2)-like 2 (NRF2) and its antioxidative signaling pathway. As a result, Cyto-IR induced mitochondria fragmentation, which accelerated the mitochondrial superoxide (MitoSOX) production. MitoSOX triggered the NRF2 nucleus translocation and upregulated the expression of its target genes, such as  heme oxygenase 1. Overall, NRF2 antioxidative response is suggested to play a key role against DNA damage under cytoplasmic irradiation.第59回日本生物物理学会年

Hypoxia and Gap Junction Communication-Induced Bystander Effect

Radiation-induced bystander effect (RIBE) has been identified as an important contributing factor to normal tissue damage and tumor development. However, the RIBE in cancer and normal cells under hypoxia remain unclear. In this study, we investigated the effect of gap junction intercellular communication (GJIC) in confluent A549 lung cancer and WI-38 normal lung cells after exposed to protons microbeam under hypoxic conditions. Following 6 hour incubation, cells were harvested and assayed for colony formation, micronucleus formation, chromosome aberration and western blotting. Our results show that there were differences of RIBE in bystander A549 and WI-38 cells under hypoxia and normoxia. The differences were also observed in the expression of HIF-1 in bystander A549 and WI-38 cells under both conditions. Interestingly, inhibition of GJIC showed a decreased in toxicity of hypoxic bystander A549 cells, but increased in hypoxic bystander WI-38 cells. We demonstrate the first time that GJIC protects bystander normal cells from toxicity while enhancing in bystander cancer cells under hypoxia.日本マイクロビーム生物研究会2021年度シンポジウ