Prolonged effect associated with inflammatory response observed after exposure to low dose of tritium β-rays

Abstract

Background: The value of relative biological effectiveness of tritium increases at low dose domain, which results in the suspicion of weighting factor of 1 for tritium after low dose exposure. Thus, present study was carried out to analyze the differences in the cellular responses at early and late period between low dose of tritium b-rays and c-rays radiation. Methods: MCF-10A cells were exposed to low dose of tritium b-rays or c-rays, then cellular behaviors, such as DNA double strand breaks (DSBs), apoptosis, reactive oxygen species (ROS) level and inflammatory relevant gene expression were analyzed at early and late period post-irradiation. Results: At early period the elimination of DSB foci produced by HTO is longer than c-rays. High ROS level and a continual change of cell cycle distribution are observed in HTO radiation group. Based on the results of RNA sequencing, Ingenuity Pathway Analysis (IPA) indicates TNFR1 signaling and production of nitric oxide and ROS are activated as an acute response at 24 h post radiation. Moreover, it also shows a disturbance in cholesterol biosynthesis. The results of 30 days point that there is a lasting active inflammatory response, accompanying with a persistent high expression of relevant cytokines, such as TNF and IL1R. Conclusion: Compared to an acute response induced by c-rays, a persistent inflammatory response exists in HTO-irradiated cells when cultured for 30 days, which might be related to accumulation of tritium in the form of organically bound tritium (OBT) in cellular DNA or lipids.

A 3D In Vitro Model of the Human Airway Epithelium Exposed to Tritiated Water: Dosimetric Estimate and Cytotoxic Effects

“…This also makes it an ideal candidate for future adoption of this model for tritiated particles, as discussed later. The persistent inflammatory response measured after exposure of mammary epithelial cells to low-dose tritium was hypothesized to be related to accumulation of tritium in the form of OBT in cellular DNA or lipids (20), though intracellular activity is measured to be very low in our case. Also, it was recently shown that, on HUVEC cells exposed to HTO (3.7 and 3,700 kBq/ml), the increase of IL-8 secretion could play a pivotal role in cell defense (21).…”

Transcriptome Analysis of the Immortal Human Keratinocyte HaCaT Cell Line Damaged by Tritiated Water

“…Shi et al found that ROS could induce the expression of SOX2 under hypoxia and then activated the activation of Wnt/ β -catenin, thus promoting the EMT of HacaT cells [ 45 ]. Quan et al proved that tritium β -rays could lead to increased ROS and the occurrence of an inflammatory reaction in breast epithelial cell line McF–10a cells [ 46 ]. Therefore, we hypothesized that the up-regulation of the Wnt pathway induced by tritiated water was related to ROS production.…”

Cyto-Genotoxicity of Tritiated Stainless Steel and Cement Particles in Human Lung Cell Models

“…Interestingly, a high level of ROS and an increase in the number of DNA double strand breaks were found in MCF-10 cells exposed to low doses of HTO [ 49 ]. Another study reported that DNA strand breaks induced by HTO in human umbilical vein endothelial cells, assessed by comet assay and γ-H2AX immunostaining, were associated with modulations of DNA repair that could be regulated by the c-myc gene expression via miR34a [ 46 ].…”