Abstract
Genome instability manifested by multiple reorganization contributes to the acquisition of new properties by tumor cells, resistance to therapy in particular. Structural rearrangements of chromosomes can be induced by damage to DNA, for example, by ionizing radiation. In this study, changes in the karyotype of the pseudodiploid cell line HindIIIG-1 obtained after irradiation of apoptosis-resistant transformed rat cells HindIIIG have been examined. The HindIIIG-1 line is a result of polyploidization associated with the cell cycle block in the G2/M phase and subsequent depolyploidization. The original HindIIIG line, before irradiation, was represented mainly by a pseudodiploid population with the normal number of 42 chromosomes, tetraploid fraction composed of 14%. The cell karyotype had two numerical and one specific structural rearrangement of chromosomes (SRCs), der(14). Irradiation induced polyploidization and multiple fragmentations of chromosomes. In the process of cultivation, a pseudodiploid population of cells with the karyotype similar to the karyotype of nonirradiated cells began to predominate, but the number of clonal and nonclonal SRCs increased. At late passages, the karyotype of HindIIIG-1 cells again became identical to the karyotype of cells before irradiation and did not contain new clonal SRCs. The role of nonclonal and clonal SRCs in the process of survival of irradiated cells and the formation of new cell populations is discussed.
Similar content being viewed by others
REFERENCES
An International System for Human Cytogenetic Nomenclature, Shaffer, Slovak, M.L. and Cambell, L.G., Eds., Basel: S. Karger, 2009.
Chitikova, Z.V., Gordeev, S.A., Bykova, T.V., Zubova, S.G., Pospelov, V.A., and Pospelova, T.V., Sustained activation of DNA damage response in irradiated apoptosis-resistant cells induces reversible senescence associated with mTOR downregulation and expression of stem cell markers, Cell Cycle, 2014, vol. 13, p. 1424. https://doi.org/10.4161/cc.28402
Crasta, K., Ganem, N.J., Dagher, R., Lantermann, A.B., Ivanova, E.V., Pan, Y., Nezi, L., Protopopov, A., Chowdhury, D., and Pellma, B., DNA breaks and chromosome pulverization from errors in mitosis, Nature, 2012, vol. 482, p. 53. https://doi.org/10.1038/nature10802
Frias, S., Ramos, S., Salas, C., Molina, B., and Rivera-Luna, S.S.R., Nonclonal chromosome aberrations and genome chaos in somatic and germ cells from patients and survivors of Hodgkin lymphoma, Genes, 2019, vol. 10, p. 1. https://doi.org/10.3390/genes10010037
Grummt, I., The Nucleolus—guardian of cellular homeostasis and genome integrity, Chromosoma, 2013, vol. 122, p. 487.
Han, J., Sabbatini, P., Perez, D., Rao, L., Modha, D., and White, E., The E1B 19K protein blocks apoptosis by interacting with and inhibiting the P53-inducible and death-promoting Bax protein, Genes Dev., 1996, vol. 10, p. 461. https://doi.org/10.1101/gad.10.4.461
Heng, H.H.Q., Regan, S, M., Liu, G., and Ye, C.J., Why it is crucial to analyze non-clonal chromosome aberrations or NCCAs?, Mol. Cytogenet., 2016, vol. 9, p. 15.
Heng, H.H., Horne, S.D., Chaudhry, S., Regan, S.M., Liu, G., Abdallah, B.Y., and Ye, C.J., A postgenomic perspective on molecular cytogenetics, Curr. Genomics, 2018, vol. 19, p. 227.
Howell, W. and Black, D.A., Controller silver staining of nucleolus organizer regions with protective colloidal developer: a one-step method, Experientia, 1980, vol. 36, p. 1014.
Jeggo, P.A. and Löbrich, M., Radiation-induced DNA damage responses, Radiat. Prot. Dosimetry, 2006, vol. 122, p. 124.
Kakarougkas, A., Ismail, A., Chambers, A.L., Riballo, E., Herbert, A.D., Künzel, J., Löbrich, M., Jeggo, P.A., and Downs, J.A., Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin, Mol. Cell, 2014, vol. 55, p. 723.
Liu, G., Stevens, J.B., Horne, S.D., Abdallah, B.Y., Ye, K.J., Bremer, S.W., Ye, C, J., Chen, D.J., and Heng, H.H., Genome chaos, survival strategy during crisis, Cell Cycle, 2014, vol. 13, p. 528. https://doi.org/10.4161/cc.27378
Ly, P. and Cleveland, D.W., Rebuilding chromosomes after catastrophe: emerging mechanisms of chromothripsis, Trends Cell Biol., 2017, vol. 27, p. 917. https://doi.org/10.1016/j.tcb.2017.08.005
Mamaeva, S.E., Regularities of cell karyotypic evolution in culture, Tsitologiia, 1996, vol. 38, p. 787.
Mamaeva, S.E., Chromosomes of human permanent cell lines, in Atlas khromosom postoyannykh kletochnykh liny cheloveka i zhivotnykh (Atlas of Chromosomes of Human and Animal Cell Lines), Moscow: Nauchnyi Mir, 2002, p. 36.
Mardin, B.R., Drainas, A.P., Waszak, S.M., Weischenfeldt, J., Isokane, M., Stütz, A, M., Raeder, B., Efthymiopoulos, T., Buccitelli, C., Segura-Wang, M., Northcott, P., Pfister, S.M., Lichter, P., Ellenberg, J., and Korbel1, J.O., A cell-based model system links chromothripsis with hyperploidy, Mol. Syst. Biol., 2015, vol. 11, p. 828. https://doi.org/10.15252/msb.20156505
Mitelman, F., Recurrent chromosome aberrations in cancer, Mutat. Res., 2000, vol. 462, p. 247.
Mitelman, F., Johansson, B., and Mertens, F., The impact of translocations and gene fusions on cancer causation, Nat. Rev. Cancer, 2007, vol. 7, p. 233.
Ohgaki, H. and Kleihues, P., Genetic alterations and signaling pathways in the evolution of gliomas, Cancer Sci., 2009, vol. 100, p. 2235.
Orsolic, I., Jurada, D., Pullen, N., Oren, M., Eliopoulos, A.G., and Volarevic, S., The Relationship between the nucleolus and cancer: current evidence and emerging paradigms, Semin. Cancer Biol., 2015. pii: S1044-579X(15)30004-3. https://doi.org/10.1016/j.semcancer.2015.12.004
Ozkinay, C. and Mitelman, F., A simple trypsin–Giemsa technique producing simultaneous G- and C-banding in human chromosomes, Hereditas, 1979, vol. 90, p. 1.
Pellestor, F.C., Chromoanagenesis: cataclysms behind complex chromosomal rearrangements, Mol. Cytogenet., 2019, vol. 12, p. 6. https://doi.org/10.1186/s13039-019-0415-7
Polyanskaya, G.G., Abramyaqn, D.S., and Glebov, O.K., The karyotypic structure of clonal population of Chinese hamster cells during a prolonged cultivation, Tsitologiia, 1981, vol. 23, p. 818.
Satoh, H., Yoshida, M.S., and Sasaki, M., Resolution chromosome banding in the Norway rat, Rattus norvegicus, Cytogenet. Cell Genet., 1989, vol. 50, p. 151.
Tuna, M., Knuutila, S., and Mills, G.B., Uniparental disomy in cancer, Trends Mol. Med., 2009, vol. 15, p. 120.
Yartseva, N.M., Fedortseva, R.F., and Artsybasheva, I.V., Chromosomal rearrangements and their effects in spontaneous immortalization and transformation of rat embryo cells in vivo, Tsitologiia, 2007, vol. 49, p. 311.
Yartseva, N.M., Bykova, T.V., Zubova, S.G., Pospelov, V.A., and Pospelova, T.V., Chromosomal instability and evolution of transformed phenotypein cell lines selected from senescent rat embryonic fibroblasts with rapamycin, Cell Tissue Biol., 2019, vol. 13, p. 18. https://doi.org/10.1134/S1990519X19010103
Ye, C.J., Regan, S., Liu, G., Alemara, S., and H.Heng, H., Understanding aneuploidy in cancer through the lens of system inheritance, fuzzy inheritance and emergence of new genome systems, Mol. Cytogenet., 2018, vol. 11, p. 31. https://doi.org/10.1186/s13039-018-0376-2
Ye, C.J., Sharpe, Z., Alemara, S., Mackenzie, S., Liu, G., Abdallah, B., Horne, S., Regan, S., and Heng, H.H., Micronuclei and genome chaos: changing the system inheritance, Genes, 2019, vol. 10, p. 366. https://doi.org/10.3390/genes10050366
Zhang, C.Z., Spektor, A., Cornils, H., Francis, J.M., Jackson, E, K., Liu, S., Meyerson, M., and Pellman, D., Chromothripsis from DNA damage in micronuclei, Nature, 2015, vol. 522, p. 179. https://doi.org/10.1038/nature14493
Funding
This work was carried out thanks to budgetary funding on a planned theme of the Institute of Cytology, Russian Academy of Sciences.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The authors declare that they have no conflict of interest.
This study did not performed experiments with animals or human beings.
Additional information
Abbreviations: ARG—amplification of ribosomal genes DSBs—double-strand breaks; SRC—structural rearrangement of chromosomes; NC—number of chromosome.
Rights and permissions
About this article
Cite this article
Yartseva, N.M., Shitikova, Z.V., Bykova, T.V. et al. Karyotypic Changes of Apoptosis-Resistant Rat Cells HindIIIG during Prolonged Cultivation after Exposure to Ionizing Irradiation. Cell Tiss. Biol. 15, 248–259 (2021). https://doi.org/10.1134/S1990519X21030135
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1990519X21030135