Ermakov A V, Kon'kova M S, Kostiuk S V, Ershova E S, Egolina N A, Veĭko N N
Radiats Biol Radioecol. 2008 Sep-Oct;48(5):553-64.
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.
我们之前已经表明，X射线辐射（10 cGy）诱导人类淋巴细胞中同源染色体位点从细胞膜转位至细胞核中心，以及染色体核仁形成区（NFR）的激活，这些反应通过DNA片段传递给未受辐射的细胞，即所谓的旁观者效应（BE）。在本研究中，在辐射前用α-生育酚阻断氧化应激（OS）或用H2O2处理均未诱导染色体位点转位或NFR激活；在存在α-生育酚的情况下，将暴露（X射线辐射或H2O2处理）淋巴细胞生长培养基中的DNA片段添加到旁观者细胞中也未诱导这些反应。此外，在抑制H2O2处理/辐射淋巴细胞中的半胱天冬酶3活性或抑制其旁观者细胞中的Toll样受体（TLR9）后，我们未观察到染色体位点的转位。基于已报道的和先前获得的研究结果，我们认为诱导的OS特异性修饰核DNA，引发辐射敏感淋巴细胞的适应性反应（AR）和凋亡机制，而由此释放的DNA片段与旁观者细胞中的TLR9相互作用最终导致OS的发生，随后是AR（BE）。本文讨论了这种途径的可能性。
