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ADAMTS1 Is Differentially Expressed in Human Lymphocytes with Various Frequencies of Endogenous γH2AX Foci and Radiation-Induced Micronuclei

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Abstract

The level of spontaneous and radiation-induced DNA damage varies depending on genetic and environmental factors in human somatic cells. This variation may be associated with transcriptional changes in cells, allowing the use of gene expression levels as markers of individual sensitivity to mutagenic effects. This study aimed to identify and characterize differentially expressed genes (DEGs) in lymphocytes of individuals with various frequencies of endogenous γH2AX foci and radiation-induced micronuclei (n = 37). The low-focus group was characterized by 0.18 ± 0.02 endogenous γH2AX foci per cell and a 155.78 ± 47.19‰ radiation-induced micronucleus frequency. The high-focus group was characterized by 0.49 ± 0.07 foci/cell and a 78.44 ± 33.21‰ micronucleus frequency. Seven DEGs (ENST00000424415, CRNDE, ADAMTS1, ENST00000424084, EIF2A, PNPLA5, and FRG2C) (FDR < 0.2) were identified by gene expression analysis with microarrays. As the extracellular matrix metalloproteinase, ADAMTS1 is able to activate the latent form of TGFβ, and TGFβ is involved in radiation-induced cellular response; the effects of ADAMTS1 knockout and overexpression on the gene expression profile were further validated in adherent HeLa cells. Twenty-nine of 160 identified DEGs are involved in apoptosis, DNA DSB repair, G2/M cell cycle transition, and the TGFβ signaling pathway. Thus, ADAMTS1 may be useful as a potential target for antitumor therapy.

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Funding

The present study was supported by the Russian Foundation for Basic Research, projects no. 14-04-31867 (experiments conducted with PBMCs of healthy individuals) and no. 19-34-90143 (experiments conducted with cell lines).

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Authors and Affiliations

  1. Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050, Tomsk, Russia

    S. A. Vasilyev, R. R. Savchenko, A. A. Belenko, N. A. Skryabin, A. A. Sleptsov & I. N. Lebedev

  2. Federal Research Center Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia

    V. S. Fishman & O. L. Serov

  3. National Research Tomsk State University, 634050, Tomsk, Russia

    A. A. Murashkina

  4. Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009, Tomsk, Russia

    O. V. Gribova & Z. A. Startseva

  5. Tomsk Regional Oncology Center, 634063, Tomsk, Russia

    E. S. Sukhikh & A. V. Vertinskiy

  6. National Research Tomsk Polytechnic University, 634050, Tomsk, Russia

    E. S. Sukhikh, A. V. Vertinskiy & L. G. Sukhikh

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  1. S. A. Vasilyev
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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

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Vasilyev, S.A., Savchenko, R.R., Belenko, A.A. et al. ADAMTS1 Is Differentially Expressed in Human Lymphocytes with Various Frequencies of Endogenous γH2AX Foci and Radiation-Induced Micronuclei. Russ J Genet 58, 1235–1244 (2022). https://doi.org/10.1134/S102279542210012X

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