Evaluation of applying γ-H2AX as a radiation biodosimetry with an animal model / 中华放射医学与防护杂志

ABSTRACT

Objective To evaluate the potential feasibility of γ-H2AX foci as a biodosimetry after exposure to ionizing radiation by comparing DNA double-strand break repair kinetics in rat blood lymphocytes with that in human lymphocytes.Methods Peripheral blood lymphocytes separated from Sprague-Dawley(SD) male rats and healthy adults were exposed to γ-rays,and some rats were also subjected to total body irradiation.The inductions of DNA repair-related foci of γ-H2AX,pATM (S1981) and pDNA-PKcs (T2609) were detected with immunofluorescence staining technique at different time points post-irradiation,and the status of their co-localization was analyzed.Results The induction kinetics of γ-H2AX foci in rat lymphocytes was similar to that observed in human lymphocytes.The frequencies of γ-H2AX foci peaked at 30 min after γ-ray irradiation (trst =62.64,th =28.52,P ＜ 0.05),then decreased rapidly after 6 h post-irradiation (trat =45.96,th =14.80,P ＜0.05),and the residual foci number remained only about 3％-8％ of its maximal value at 24 h post-irradiation.At 30 min after γ-ray irradiation,the frequencies of pATM (S1981) and pDNA-PKcs (T2609) foci in rat and human lymphocytes significantly higher than those of nonirradiated control (trat =21.05,25.80,th =11.07,29.52,P ＜ 0.05),and the frequencies of co-localization of pATM (S1981) or pDNA-PKcs (T2609) foci with γ-H2AX foci also markedly increased by 26％-32％ in irradiated lymphocytes of rat and human (trat =5.34,9.14,thuman =18.32,51.28,P ＜0.05).Moreover,γ-H2AX foci incidence in rat lymphocytes in vitro was consistent with that induced by total body irradiation of rat.The number of γ-H2AX foci in irradiated rat lymphocytes increased with irradiation dose in a linear dose-dependent manner,its slope was similar to that of irradiated human lymphocytes reported by other laboratory.Conclusions Rat is a useful animal model to evaluate radiation biodosimetry with γ-H2AX foci in lymphocytes.The co-activation of ATM and DNA-PK plays an important role in DSB repair in the irradiated lymphocytes of rat and human.