Abstract
Nuclear factor κB (NF-κB) activation might be central to heavy ion-induced detrimental processes such as cancer promotion and progression and sustained inflammatory responses. A sensitive detection system is crucial to better understand its involvement in these processes. Therefore, a DD-tdTomato fluorescent protein-based reporter system was previously constructed with human embryonic kidney (HEK) cells expressing DD-tdTomato as a reporter under the control of a promoter containing NF-κB binding sites (HEK-pNFκB-DD-tdTomato-C8). Using this reporter cell line, NF-κB activation after exposure to different energetic heavy ions (16O, 95 MeV/n, linear energy transfer—LET 51 keV/µm; 12C, 95 MeV/n, LET 73 keV/μm; 36Ar, 95 MeV/n, LET 272 keV/µm) was quantified considering the dose and number of heavy ions hits per cell nucleus that double NF-κB-dependent DD-tdTomato expression. Approximately 44 hits of 16O ions and ≈45 hits of 12C ions per cell nucleus were required to double the NF-κB-dependent DD-tdTomato expression, whereas only ≈3 hits of 36Ar ions were sufficient. In the presence of Shield-1, a synthetic molecule that stabilizes DD-tdTomato, even a single particle hit of 36Ar ions doubled NF-κB-dependent DD-tdTomato expression. In conclusion, stabilization of the reporter protein can increase the sensitivity for NF-κB activation detection by a factor of three, allowing the detection of single particle hits’ effects.
Highlights
X-rays was determined by means the reporter line human embryonic kidney (HEK)-pNFκB-destabilizing domain (DD)-tdTomato-C8, a determined meansand of the cell line
Ground-based experiments with high-linear energy transfer (LET) heavy ions were performed with clear evidence that a single particle hit can induce Nuclear factor κB (NF-κB)-mediated cellular responses
In the presence of Shield-1, the fluorescent protein DD-tdTomato was accumulated inside the cell, which helped to quantify the fold induction of the promoter containing NFκB-binding sites after heavy ion exposure
Summary
Astronauts are chronically exposed to galactic cosmic rays at a low dose rate. Heavy ions make up only about 2% of the fluence in space. Payload limitations in spacecraft design, the production of secondary particles in shielding material, and long durations of deep space travel impede in completely removing the probability of exposure to such heavy ions. Heavy ions are gaining wider popularity for clinical use to effectively target and treat solid malignancies. Further study of the biological effects of heavy ions is vital to improve the health effects
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