Differences in sustained alterations in protein expression between livers of mice exposed to high-dose-rate and low-dose-rate radiation

Abstract

Molecular mechanisms of radiation dose-rate effects are not well understood. Among many possibilities, long-lasting sustained alterations in protein levels would provide critical information. To evaluate sustained effects after acute and chronic radiation exposure, we analyzed alterations in protein expression in the livers of mice. Acute exposure consisted of a lethal dose of 8 Gy and a sublethal dose of 4 Gy, with analysis conducted 6 days and 3 months after irradiation, respectively. Chronic irradiation consisted of a total dose of 8 Gy delivered over 400 days (20 mGy/day). Analyses following chronic irradiation were done immediately and at 3 months after the end of the exposure. Based on antibody arrays of protein expression following both acute lethal and sublethal dose exposures, common alterations in the expression of two proteins were detected. In the sublethal dose exposure, the expression of additional proteins was altered 3 months after irradiation. Immunohistochemical analysis showed that the increase in one of the two commonly altered proteins, MyD88, was observed around blood vessels in the liver. The alterations in protein expression after chronic radiation exposure were different from those caused by acute radiation exposures. Alterations in the expression of proteins related to inflammation and apoptosis, such as caspase 12, were observed even at 3 months after the end of the chronic radiation exposure. The alterations in protein expression depended on the dose, the dose rate, and the passage of time after irradiation. These changes could be involved in long-term effects of radiation in the liver.

Radiation-Induced Reactions in the Liver—Modulation of Radiation Effects by Lifestyle-Related Factors—

“…Apoptosis was suggested to have a kind of repressive function in liver carcinogenesis [38]. Alteration of apoptosis-related proteins may imply that radiation-induced protective abilities persist following damage from radiation [36]. We have also detected the induction of rhodanese, a participant in sulfur metabolism, following low-dose-rate, long-term irradiation.…”

“…Other studies have examined alterations to protein expression [35,36]. In particular, proteins related to inflammation or apoptosis seem to contribute to the effects of irradiation on the liver [36,37]. High-dose radiation usually induces inflammation, leading to fibrosis or cancer.…”

“…High-dose radiation usually induces inflammation, leading to fibrosis or cancer. Interestingly, mice irradiated acutely at high doses (4Gy or 8Gy) showed persistent alterations to expression of proteins related to inflammation, whereas a total dose of 8Gy by low-dose-rate, long-term irradiation induced alteration of expression for many apoptosis-related proteins [36]. Apoptosis was suggested to have a kind of repressive function in liver carcinogenesis [38].…”

Life-Shortening Effect of Chronic Low-Dose-Rate Irradiation in Calorie-Restricted Mice

“…Recent comparative studies on the molecular alterations induced by acute and chronic radiation exposure revealed certain quantitative and qualitative differences (11,12,(15)(16)(17). For example, Nakajima et al (17) compared the mouse liver proteins affected by acute 4 Gy and chronic 8 Gy (20 mGy/day 3 400 days) radiation using an antibody microarray assay. They examined the alterations three months postirradiation and found that the affected proteins were completely different between the two groups.…”

Effects of low dose and low dose rate low linear energy transfer radiation on animals – review of recent studies relevant for carcinogenesis

“…For example, liver protein expression was evaluated in C57BL/6J male mice after chronic daily gamma ray exposures done at IES versus acute x-ray exposures at high dose rate. Chronic, 400 days long exposures to gamma rays included dose rate of 1 mGy per day (total dose of 0.4 Gy) or 20 mGy per day (total dose of 8 Gy); while acute x-ray exposures included 4 or 8 Gy given to 10-or 24-week old animals (Nakajima et al 2017). Chronically exposed mice were sacrificed immediately or 3 months after exposure, and the acutely exposed mice 6 days or 3 months after radiation delivery.…”