Abstract
Purpose: Analysis of the relative expression of radiation responsive genes (previously shown to respond to γ-radiations) after exposure of human lymphocytes to 211At α-particles and the suitability of these genes as potential markers for α-biodosimetry.Materials and methods: Lymphocytes isolated from the peripheral blood of two healthy human donors were exposed in triplicate for 30 min to different concentrations of Na211At at 37°C (absorbed doses: 0.05–1.6 Gy). Following an incubation period (2 h), the total RNA was isolated from the irradiated lymphocytes and the relative expression of the following 18 genes was tested for change using TaqMan™ probes based upon the real-time quantitative polymerase chain reaction.Method: BBC3 (B-cell lymphoma 2 binding component 3), CD69 (cluster of differentiation 69), CDKN1A (cyclin-dependent kinase inhibitor 1A), DUSP8 (dual specificity phosphatase 8) EGR1 (early growth response 1), EGR4 (early growth response 4), GADD45A (growth arrest and DNA-damage-inducible, alpha), GRAP (growth factor receptor-bound protein 2-related adaptor protein), LAP1B (TOR1AIP1; torsin A interacting protein 1), IFNG (interferon gamma), ISG20L1 (interferon-stimulated exonuclease gene 20kDa – like 1), c-JUN (jun oncogene), MDM2 (mouse double minute 2), PCNA (proliferating cell nuclear antigen), PLK2 (polo-like kinase 2), RND1 (rho family GTPase 1), TNFSF9 (tumour necrosis factor superfamily member 9) and TRAF4 (tumour necrosis factor receptor-associated factor 4).Results: The expressions of the 18 genes, except GRAP, were up-regulated following exposure to α-radiation. A comparison of the results of two individuals tested here showed great variability. Dependence of gene expression upon α-dose was observed in certain dose intervals for BBC3 (R2 = 0.61 [individual 1] / 0.81 [individual 2], significance 0.2–1.6 Gy [1] / 0.05–0.1 Gy [2]) and MDM2 (R2 = 0.78/0.54; 0.8–1.6 Gy [1], 0.05–0.1 Gy [2]) genes in both individuals. Additionally, for individual 1 the dose dependence was found for the following genes: ISG20L1 (R2 = 0.69, 0.05–0.1 Gy), PCNA (R2 = 0.59, 0.8–1.6 Gy) and IFNG (R2 = 0.74 up to 0.4 Gy, 0.05–0.1 Gy).Conclusion: Candidate genes for a possible role in future early-phase (2 h) α-biodosimetry are BBC3, ISG20L1, MDM2, PCNA and IFNG.
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