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

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 β-rays and γ-rays radiation.Methods: MCF-10A cells were exposed to low dose of tritium β-rays or γ-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 γ-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 γ-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.