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

Objective: To study the time-and dose-effect of mitochondrial DNA (mtDNA) 4934 bp and 4977 bp deletions in the human peripheral blood irradiated by ¹³⁷Cs 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 dose-effect 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 48 h 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 dose-dependent 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 Ŷ₁ = 1.178 + 0.1219D (R² = 0.9269) and Ŷ₂ = 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. (authors)