Cyclooxygenase‑2‑mediated upregulation of heme oxygenase 1 mitigates the toxicity of deuterium‑tritium fusion radiation

Abstract

Utilizing the energy released from the nuclear fusion of deuterium with tritium (D-T) may be an important method of supplying energy in the future. The ionizing radiation emitted from nuclear fusion is a potential health risk to humans, including scientists who are currently performing nuclear fusion experiments and the employees of fusion nuclear plants, in the future. However, there have been few reports on the biological effects of fusion radiation. In the present study, using the High Intensity D-T Fusion Neutron Generator, the DNA damage and its regulation in normal human fibroblasts exposed to fusion radiation were investigated. Heme oxygenase 1 (HO-1), which is reported to induce anti-inflammatory activity, was upregulated in the irradiated cells. Pretreatment with the HO-1 inhibitor, protoporphyrin IX zinc (II), exacerbated double strand break formation following exposure to fusion radiation. The expression of cyclooxygenase-2 (COX-2) contributed to the upregulation of HO-1, as demonstrated by the result that its inhibitor, NS-398, inhibited the induction of HO-1 in irradiated cells. It was further clarified that the ataxia telangiectasia mutated DNA damage response was activated and it stimulated the phosphorylation of p38 mitogen-activated protein kinase, which was responsible for the upregulation of COX-2 and HO-1. These results provide novel information on fusion radiation-induced biological effects and potential targets for decreasing the associated health risks.

The COX-2/PGE2 Response Pathway Upregulates Radioresistance in A549 Human Lung Cancer Cells through Radiation-Induced Bystander Signaling

“…The time course of the transmission and amplification process is unknown, but it is an important parameter in RIBE. Moreover, based on the reports of others [31][32][33][34] and our results, we considered that variations in downstream cellular defense mechanisms might arise depending on the initial levels of PGE2 production.…”

“…Indeed, others have reported that COX-2 and PGE2 are potentially involved in the induction of downstream cellular stress defense mechanisms. For example, PGE2 has been shown to induce the oxidative stress defense mechanism by HO-1 activation, which is a downstream gene of Nrf2 via COX-2/PGE2 [31,32]. Also, it is reported that COX-2 expression upregulates defensively against radiation-induced DNA damage and suppression of apoptosis through activation of multiple pathways such as STAT3, HIF-1α/PKM2 pathway [33,34].…”

Glycofullerenes as non-receptor tyrosine kinase inhibitors- towards better nanotherapeutics for pancreatic cancer treatment

“…Under normal conditions, HO-1 expression is low in the majority of cells and tissues. Some reports have demonstrated that upregulation of HO-1 is regulated by signaling pathways, in which MAPK kinases play a key role 37,38 . With this in mind, we have evaluated HO-1 levels after 24-and 72-hour treatment with glycofullerenes (Fig.…”