Extracellular DNA fragments from culture medium of low-dose irradiated human lymphocyte trigger instigating of the oxidative stress and the adaptive response in non-irradiated bystander lymphocytes

• Published in: Radiat͡s︡ionnai͡a︡ biologii͡a︡, radioėkologii͡a Vol. 48; no. 5; p. 553
• Main Authors: Ermakov, A V, Kon'kova, M S, Kostiuk, S V, Ershova, E S, Egolina, N A, Veĭko, N N
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01.09.2008
• Subjects: Bystander Effect - radiation effects; Cells, Cultured; Culture Media - chemistry; DNA - analysis; DNA - radiation effects; DNA Damage; Dose-Response Relationship, Radiation; Gamma Rays - adverse effects; Gene Expression - radiation effects; Humans; In Situ Hybridization, Fluorescence; Lymphocytes - cytology; Lymphocytes - metabolism; Lymphocytes - radiation effects; Myeloid Differentiation Factor 88 - genetics; Oxidative Stress - radiation effects; Polymerase Chain Reaction; Toll-Like Receptor 9 - genetics
• ISSN: 0869-8031

We have previously shown that the induced by X-ray radiation (10 cGy) in human lymphocytes reactions of transposition of the loci of homologous chromosomes from the membrane to the centre of the nucleus, and activation of the chromosomal nucleolus-forming regions (NFR) are transmitted via DNA fragments to the nonirradiated cells--the so-called bystander effect (BE). In the present study, the blockade of the oxidative stress (OS) with alpha-tocopherol prior to irradiation or treatment with H2O2 induced no effects of either chromosomal loci transposition or activation of the NFR; neither in the presence of alpha-tocopherol were these reactions induced by the addition of the DNA fragments from the growth medium of the exposed (X-irradiated or H2O2-treated) lymphocytes to the bystander cells. Moreover, after inhibiting the activity of caspase 3 in the H2O2-treated/irradiated lymphocytes or suppression of the toll-like receptors (TLR9) in their bystander cells, we observed no transposition of the chromosomal loci. Based on the reported and previously obtained findings we suggest that the induced OS specifically modifies nuclear DNA, instigating the mechanisms of the adaptive response (AR) and apoptosis of the radiation-sensitive lymphocytes, while the interaction of the DNA fragments released therefrom with the TLR9 of the bystander cells leads to the development of the OS in last, to be followed by the AR (BE). Possibilities of such a pathway are discussed herein.