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Relationship between micronucleus formation and oxidative stress in human vascular endothelial cells under low dose rate irradiation

Fundamental Toxicological Sciences(2022)

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摘要
Acute irradiation stimulates oxidative stress and DNA damage responses. However, it is unknown whether chronic irradiation (IR) at a low dose rate causes similar responses, and epidemiological studies of radiation-exposed people with low doses have reported effects on cardiovascular diseases. Therefore, we investigated the cellular effects under low dose rate of IR in human vascular endothelial cells as a model for cardiovascular diseases. We demonstrated that a low dose rate of IR induces phosphorylation of p38MAPK and STAT1, which is related to cGAS, and increases p21, a cellular senescence-regulatory factor. A low dose rate of IR also causes a remarkable formation of micronuclei in human vascular endothelial cells. DIA proteome analysis in human vascular endothelial cells indicated an increase in oxidative stress- and inflammation-related protein levels, and a decrease in protein levels related to the repression of micronuclei formation following exposure to low dose rate of IR. These results suggest that a low dose rate of IR might induce oxidative stress and micronuclei formation, which could activate the cGAS pathway and subsequently lead to cellular senescence.
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关键词
human vascular endothelial cells,oxidative stress,irradiation,micronucleus formation
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