Purpose: Analysis of the relative expression of radiation responsive genes (previously shown to respond to gamma-radiations) after exposure of human lymphocytes to (211)At alpha-particles and the suitability of these genes as potential markers for alpha-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 Na(211)At at 37 degrees 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 alpha-radiation. A comparison of the results of two individuals tested here showed great variability. Dependence of gene expression upon alpha-dose was observed in certain dose intervals for BBC3 (R(2) = 0.61 [individual 1] / 0.81 [individual 2], significance 0.2-1.6 Gy [1] / 0.05-0.1 Gy [2]) and MDM2 (R(2) = 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 (R(2) = 0.69, 0.05-0.1 Gy), PCNA (R(2) = 0.59, 0.8-1.6 Gy) and IFNG (R(2) = 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) alpha-biodosimetry are BBC3, ISG20L1, MDM2, PCNA and IFNG.