Inflammatory mediator-induced bystander effects and genomic instability: role of tissue-specificity

Abstract

Much evidence showed that radiation-induced inflammation can cause cellular damage in direct irradiated and bystander cells, which are in vicinity of irradiated cells underlying radiation-induced bystander effects (BE). As well as radiation-induced genomic instability (GI) is observed within the progeny of irradiated and bystander cells as a delayed damage responses. This study tried to mimic the effects of radiation-induced GI and BE by exploring the inflammatory effect of lipopolysaccharide (LPS) on human primary fibroblast (HF 19) and umbilical vein endothelial (HUVEC) cells. To prove the principles of LPS can cause DNA damage in HF 19; cells were treated with 1 μg/ml LPS, and BE was induced by media transfer. Comet assay was used to estimate DNA damage in the direct treated and bystander cells. The early DNA damage result was significantly observed in the direct treated and bystander HF 19 cells. However, these cells did not show a significant delayed DNA damage within their progeny. Comet data showed that LPS frequently induced only initial DNA damage in HF 19 cells. The experiment was repeated utilising HF 19 and HUVEC cells, in order to investigate whether LPS could be involved in the induction of GI in a tissue-specificity manner. Both HF 19 and HUVEC cells were treated with 1 μg/ml LPS. BE was also induced by media transfer. Chromosomal analysis was used for early and late chromosomal damage estimation. Data showed that LPS treatment could significantly cause early chromosomal aberrations in the direct treated and bystander HF 19 and HUVEC cells. However, delayed chromosomal instability was observed only in the direct treated HUVEC cells. Our finding suggested that LPS frequently induced BE in HF 19 and HUVEC cells, which could be mediated by pro-inflammatory cytokines that stimulated by LPS treatment. Moreover, LPS could be involved in the GI induction in a tissue-specificity manner.Keywords: