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

Abstract

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.