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Comparative analysis of natural and synthetic antimutagens as regulators of gene expression in human cells under exposure to ionizing radiation

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Abstract

This paper studies the effect of plant peptides of thionine Ns-W2 extracted from seeds of fennel flower (Nigella sativa) and β-purothionine from wheat germs (Triticum kiharae), as well as a synthetic antimutagen (crown-compound), on the expression of several genes involved in the control of cellular homeostasis, processes of carcinogenesis, and radiation response in human rhabdomyosarcoma cells (RD cells), T-lymphoblastoid cell line Jurkat, and blood cells. All of these agents acted as antimutagens-anticarcinogens, reducing the expression of genes involved in carcinogenesis (genes of families MMP, TIMP, and IAP and G-protein genes) in a tumor cell. A pronounced reduction in the mRNA level of these genes was caused by thionine Ns-W2, and the least effect was demonstrated by β-purothionine. Antimutagens had very little effect on the mRNA levels of the several studied genes in normal blood cells. Thionine Ns-W2 in tumor cells resulted in a reduction of the content of oncogenic mature miR-21 but did not affect the mRNA level of gene p53 and mature miR-34, which was regulated by the activity of tumor suppressor p53. It was established that thionine Ns-W2 has a cytotoxic effect by inducing the death of RD cells and lymphoma. The exposure of these cells to ionizing radiation enhanced the inhibitory effect of thionine on expression of the genes involved in oncogenesis. These data indicate that thionine can be regarded as a promising anticarcinogen.

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Correspondence to V. F. Mikhailov.

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Original Russian Text © V.F. Mikhailov, A.A. Shishkina, I.M. Vasilyeva, L.V. Shulenina, N.F. Raeva, E.A. Rogozhin, M.I. Startsev, G.D. Zasukhina, S.P. Gromov, M.V. Alfimov, 2015, published in Genetika, 2015, Vol. 51, No. 2, pp. 147–155.

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Mikhailov, V.F., Shishkina, A.A., Vasilyeva, I.M. et al. Comparative analysis of natural and synthetic antimutagens as regulators of gene expression in human cells under exposure to ionizing radiation. Russ J Genet 51, 130–137 (2015). https://doi.org/10.1134/S102279541411009X

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  • DOI: https://doi.org/10.1134/S102279541411009X

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