Time-and dose-effect of mitochondrial DNA deletions in γ-ray irradiated human peripheral blood

Abstract

Objective To study the time-and dose-effect of mitochondrial DNA (mtDNA) 4934 bp and 4977 bp deletions in the human peripheral blood irradiated by137 Cs γ-rays,and to evaluate its implication in biological dosimetry.Methods The peripheral blood from five healthy adults was collected and irradiated with γ-rays.The peripheral blood of one healthy adult was irradiated with 5 Gy and cultured for 2,24,48 and 72 h after irradiation.The peripheral blood from the other four healthy adults was cultured for 2 h after 0,0.5,1,2,5 and 10 Gy irradiation.The peripheral blood mtDNA 4934 bp and 4977 bp deletions were detected by real-time polymerase chain reaction and gel electrophoresis.The doseeffect curves were fitted using Curve Expert 1.4 Software.Results mtDNA 4934 bp and 4977 bp deletions were induced at 2 h post-irradiation and the mtDNA 4934 bp deletion had relative high levels at 2 h and 48h after radiation (t =10.782 and 8.966,P ＜ 0.05),and mtDNA 4977 bp deletion reached the highest level at 48 h after radiation (t =7.433,P ＜0.05).mtDNA 4934 bp (t =2.895-8.105,P ＜0.05) and 4977 bp deletion (t =3.006-7.715,P ＜0.05) irradiated at 0.5-10 Gy increased with a dosedependent manner.The incidence of mtDNA 4977 bp deletion was higher than that of 4934 bp deletion for those samples exposed with same dose of irradiation,especially at 10 Gy (t =2.919,P ＜ 0.05),which suggested that 4977 bp deletion might be more sensitive than 4934 bp deletion at high dose.But larger individual differences were found in 4977 bp deletion compared with 4934 bp deletion.The dose-effect equations for 4934 bp deletion and 4977 bp deletion were Y1 =1.178 + 0.1219D (R2 =0.9269) and Y2 =1.2578 +0.1933D (R2 =0.9016),respectively.Conclusions The induction of mtDNA deletion was correlated with radiation dose,and thus it may be a available method for biological dose estimation and prognostic evaluation. Key words: Ionizing radiation ; Mitochondrial DNA deletions ; 4934bp deletion; Time-effect; Dose-effect