Alteration of gene expression in mice exposed to long-term low dose-rate radiation

Abstract

Biological responses to low dose radiation are not well understood. Above all, responses to low dose-rate irradiation such as 20 to 500 mGy per year have special meaning because the dose level corresponds to the dose limit of radiation workers or the exposure level of astronauts in space. Here, we have challenged to obtain molecular clues to understand biological responses to long-term low dose-rate radiation. C57BL/6J mice were irradiated continuously for 401 or 485 days at the dose rates of 38 or 32 nGy/min, 767 or 650 nGy/min, or 15.3 or 12.5 µGy/min. The total doses were about 20 mGy, 400 mGy or 8 Gy. Immediately after irradiation, liver and kidney were examined for alteration in gene expression. Microarray analysis of liver RNA showed that the levels of some mRNAs changes at the three dose ranges used. RT-PCR analysis confirmed the changes. Proteome analysis showed an increase of one mitochondrial protein at middle and high doses. Since mRNA level of the protein remained unchanged as judged by microarray analysis, the increase would be post-translational effect. Microarray analysis of kidney RNA also showed alterations in about 50 kinds of mRNA. Among them, 4 mRNAs which are involved in oxidative phosphorylation in mitochondria were found to be elevated by irradiation. These results suggest a presence of some kinds of effects at gene expression level. However, physiological meanings of these molecular changes are yet to be proved.