Epigenetics of health and disease

Biology 4110: Advances in Genetics, Molecular and Cell Biology

Olga Kovalchuk's Laboratory - Publications

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Articles submitted on in the final stages of preparation for submission


L. Luzhna , A. Golubov , I. Pogribny and O. Kovalchuk. Molecular mechanisms of radiation resistance in doxorubicin-resistant breast adenocarcinoma cells. DNA Repair , in revision.

O. Kovalchuk , F. Zemp , J. Filkowski , J.S. Dickey, G. Jenkins-Baker , S. A. Marino, D .J. Brenner, W.M. Bonner, O.A. Sedelnikova. microRNAome changes in bystander 3D human tissue models suggest priming of apoptosis. Carcinogenesis , submitted .

I. Koturbash , F. Zemp , B. Kolb and O. Kovalchuk . Sex-specific radiation-induced microRNAome responses in the hippocampus, cerebellum and frontal lobe in a mouse model. Mutation Research , submitted.

Articles in refereed journals published or in press:


•  I.P. Pogribny, J. Filkowski , V.P. Tryndyak, S.I. Shpyleva and O. Kovalchuk . Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. International Journal of Cancer , in press.

•  L.Luzhna and O.Kovalchuk . Modulation of DNA methylation levels sensitizes doxorubicin-resistant breast adenocarcinoma cells to radiation-induced apoptosis. Biochem Biophys Res Commun, in press.

•  J.Filkowski, Y. Ilnytsky, T. Bagnyukova, I. Koturbash, I. Pogribny and O. Kovalchuk. Hypomethylation and genome instability in the germline of exposed parents and their progeny is associated with altered miRNA expression. Carcinogenesis , in press.

•  I. Koturbash, F. J. Zemp, I. Pogribny and O. Kovalchuk. Small molecules with big effects:The role of the microRNAome in cancer and carcinogenesis. Mutation Research , in press.

•  I. Koturbash , J. Thomas, O. Kovalchuk , I. Kovalchuk. Heat-killed bacteria induce genome instability in the gut and in distant spleen and liver tissues. Cell Cycle 2009; 8: 1935-9

•  S. Ilnytskyy , I. Koturbash and O. Kovalchuk. Radiation-induced bystander effects in vivo are epigenetically regulated in a tissue-specific manner. Environmental and Molecular Mutagenesis 2009; 50:105-13. Editor's choice paper.


•  J. Tamminga , P. Kathiria , I. Koturbash , O. Kovalchuk . DNA damage-induced upregulation of miR-709 in the germline downregulates BORIS to counteract aberrant DNA hypomethylation. Cell Cycle 2008 7:3731-3766. Editor's choice paper.

•  Y. Ilnytskyy , F.J. Zemp , I. Koturbash , O. Kovalchuk Altered microRNA expression patterns in irradiated hematopoietic tissues suggest a sex-specific protective mechanism. Biochem Biophys Res Commun . 377:41-45.

•  O. Kovalchuk , J. Filkowski , J. Meservy , Y.Ilnytskyy , V. Tryndyak, V. Chekhun and I. Pogribny. Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Molecular Cancer Therapeutics 7: 2152-2159.

•  I. Koturbash , K. Kutanzi, R. Rodriguez-Juarez, D. Kogosov and O. Kovalchuk . Distinct epigenetic manifestations of the in vivo radiation-induced bystander effects in male and female mice. Mutation Research 642: 28-36.

•  I.Koturbash , F.J. Zemp , K. Kutanzi , L. Luzhna , J. Loree , B. Kolb and O. Kovalchuk. Sex-specific microRNAome deregulation in the shielded bystander spleen of cranially exposed mice. Cell Cycle 7: 1658-67.

•  J .Tamminga, I. Koturbash , M. Baker , K. Kutanzi , P. Kathiria , I. Pogribny, R. Sutherland and O. Kovalchuk . Paternal cranial exposure induces distant bystander damage in the germline and leads to epigenetic alterations in the offspring. Cell Cycle 7: 1238-45. COVER PAGE PICTURE.

•  C. Yauk, A. Polyzos, A. Rowan-Carroll, C.M. Somers, R.W. Godschalk, F J. Van Schooten, M.L. Berndt, I.P. Progribny, I. Koturbash , A. Williams, G.R. Douglas, O. Kovalchuk . Germline Mutations, DNA Damage and Global Hypermethylation in Mice Exposed to Particulate Air Pollution in an Urban/Industrial Location. Proceedings of the National Academy of Sciences of the USA 105:605-10

•  I. Koturbash , J. Loree , K. Kutanzi , C. Koganow , I. Pogribny, and O. Kovalchuk . In vivo bystander effect: cranial X-irradiation leads to elevated DNA damage and altered cellular proliferation and apoptosis in shielded spleen. International Journal of Radiation Oncology*Biology*Physics 70: 554-62 .

•  O. Kovalchuk . Epigenetic research sheds new light on the nature of interactions between organisms and their environment. Environmental and Molecular Mutagenesis 49:1-3.

•  O. Kovalchuk , J.E. Baulch. Epigenetic changes and non-targeted radiation effects – is there a link? Environmental and Molecular Mutagenesis 49:16-25

•  C.L. Yauk, A.Polyzos, A.Rowan-Carroll, I. Kortubash , A. Williams, O. Kovalchuk . Tandem repeat mutation, global DNA methylation and regulation of DNA methyltransferases in cultured mouse embryonic stem cells chronically exposed to chemicals with different modes of action. Environmental and Molecular Mutagenesis 49:26-35.


•  O. Kovalchuk , V. P. Tryndyak, B. Montgomery, A. Boyko , R. Rodriguez-Juarez , F.Zemp , A.R. Warbritton, J.R. Latendesse, I. P. Pogribny. Estrogen-induced rat breast carcinogenesis is characterized by alterations of DNA methylation, histone modifications and aberrant microRNAs expression. Cell Cycle 6: 2010-2018.

•  I. Pogribny, T.V. Bagnyukova, V.P. Tryndyak, L. Muskhelishvili, R. Rodriguez-Juarez , O. Kovalchuk , T. Han, J.C. Fuscoe, F.A. Beland. Gene expression profiling reveals the underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis. Toxicol Appl Pharmacol. 225:61-69.

•  Kovalchuk I, Molinier J, Yao Y, Arkhipov A, Kovalchuk O . Transcriptome analysis reveals fundamental differences in plant response to acute and chronic exposure to ionizing radiation. Mutation Research 624:101-13.

•  I. Koturbash , A. Boyko , R. Rodriguez-Juarez , R. McDonald, V. Tryndyak, I. Kovalchuk, I. Pogribny and O. Kovalchuk . Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo. Carcinogenesis 28, 1831-1838.

•  O. Sedelnikova, A. Nakamura, O. Kovalchuk , I. Koturbash , S. Mitchell, S. Marino, D. Brenner, W. Bonner DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Cancer Research 67, 4295-4302.

•  I. Pogribny, V. Tryndyak, A.Boyko , R. Rodriguez-Juarez, F.A. Beland and O. Kovalchuk . MicroRNAome deregulation in tamoxifen-induced rat liver carcinogenesis. Mutation Research 619, 30-37.

•  V. F. Chekhun, N. Y. Lukyanova, V.P. Tryndyak, O. Kovalchuk and I. P. Pogribny. Epigenetic profiling of multidrug resistant breast cancer cells reveals novel hypo- and hypermethylated targets. Molecular Cancer Therapeutics 6, 1089-1098.

•  Tryndyak VP, Kovalchuk O , Muskhelishvili L, Montgomery B, Rodriguez-Juarez R , Melnyk S, Ross SA, Beland FA, Pogribny IP. Epigenetic reprogramming of liver cells in tamoxifen-induced rat hepatocarcinogenesis. Molecular Carcinogenesis 46, 187-197.


•  J. Loree , I. Koturbash , K. Kutanzi , M. Baker , I. Pogribny, and O. Kovalchuk . Radiation-induced DNA damage and epigenetic changes in rat mammary tissue: possible implications for radiation-induced carcinogenesis. International Journal of Radiation Biology 82, 805-815.

•  O. Kovalchuk , V. F. Chekhun and I. P. Pogribny. Role of microRNAome changes in drug resistance of breast cancer cells. Oncology , 11, 75.

•  I. Koturbash , M. Baker , J. Loree , K. Kutanzi , D. Hudson , I. Pogribny, O. Sedelnikova, W. Bonner and O. Kovalchuk . Epigenetic Dysregulation Underlies the Transgenerational Genome Instability in vivo. International Journal of Radiation Oncology*Biology*Physics 66, 327-330

•  V. P Tryndyak, O. Kovalchuk and I. P. Pogribny. Identification of differentially methylated sites within unmethylated DNA domains in normal and breast cancer cells. Analytical Biochemistry 356, 202-207.

•  V. P. Tryndyak, L. Muskhelishvili, O. Kovalchuk , R. Rodriguez-Juarez , B. Montgomery, S. A. Ross, M. I. Churchwell, F. A. Beland, I.P. Pogribny. Effect of long-term tamoxifen exposure on genotoxic and epigenetic changes in rat liver: implications for tamoxifen-induced hepatocarcinogenesis . Carcinogenesis 27, 1713-1720.

•  I. Koturbash , R.E. Rugo, C.A. Hendricks, J. Loree , B. Thibault , K. Kutanzi , I. Pogribny, J.C. Yanch, B.P. Engelward, and O. Kovalchuk . Irradiation induces DNA damage and modulates epigenetic effectors in distant bystander tissue in vivo . Oncogene 25, 4267-4275

•  V. Tryndyak, O. Kovalchuk , I. Pogribny (2006) Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4-20h2 histone methyltransferase and methyl-binding proteins. Cancer Biology and Therapy 5, 65-70.

•  I. Koturbash , S. Cassie, M. Baker , Y. Ilnitsky , D. Hudson , E. Weber and O. Kovalchuk . Novel retinoblastoma binding protein RBBP9 modulates sex-specific radiation responses in vivo . Carcinogenesis 27, 465-474


•  I. Pogribny, I. Koturbash , V. Tryndyak, D. Hudson, S.M. Stevenson , O. Sedelnikova, W. Bonner and O. Kovalchuk (2005) Fractionated low-dose radiation exposure leads to accumulation of DNA damage and profound alterations in DNA and histone methylation in the murine thymus. Molecular Cancer Research 3, 553-561.

•  I. Koturbash , I. Pogribny, O. Kovalchuk (2005) Stable loss of global DNA methylation in the radiation-target tissue-A possible mechanism contributing to radiation carcinogenesis? Biochem Biophys Res Commun . 337, 526-533.

•  J. Besplug , A. Ponton, J. Filkowski , I. Kovalchuk and O. Kovalchuk . (2005) Sex differences in the low-dose radiation–induced oncogenic signaling. Int. J. Radiat. Biol . 81, 157-168.

•  I. Kovalchuk, V. Titov , B. Hohn and O. Kovalchuk (2005) Transcriptome profiling reveals similarities and differences in plant responses to cadmium and lead. Mutat Res . 570, 149-161


•  G. Silasi , R. Diaz-Heijtz, J. Besplug , R. Rodriguez-Juarez , V. Titov , B. Kolb and O. Kovalchuk (2004) Selective brain responses to acute and chronic low dose X-ray irradiation in males and females. Biochem Biophys Res Commun 325, 1223-1235.

•  J. Raiche , R. Rodriguez-Juarez , I. Pogribny and O. Kovalchuk (2004) Sex and tissue specific expression of maintenance and de novo DNA methyltransferases upon low dose X-irradiation in mice. Biochem Biophys Res Commun 325, 39-47

•  O. Kovalchuk , C.A. Hendricks, S. Cassie , A.J. Engelward and B.P. Engelward (2004) In vivo recombination after chronic damage exposure falls to below spontaneous levels in ‘Recombomice'. Molecular Cancer Research 2, 567-573 .

•  I. Pogribny, J. Raiche , M. Slovack and O. Kovalchuk (2004) Dose-dependence, sex- and tissue-specificity and persistence of radiation-induced genomic DNA methylation changes. Biochem Biophys Res Commun 320, 1253-1260

•  Kovalchuk O. , P onton A. , Filkowski J and Kovalchuk I. (2004) Dissimilar genome response to acute and chronic low dose radiation in male and female mice. Mutation Research 550, 59-72.

•  Kovalchuk O., Burke P. , Besplug J. Slovack M ., Filkowski J. and Pogribny I. (2004) Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low dose X-ray-irradiation. Mutation Research 548, 75-84.

•  Kovalchuk, I. , Pelczar, P. and Kovalchuk, O. (2004) The high frequency of nucleotide misincorporations upon the processing of the double-strand breaks. DNA repair 3, 217-223.

•  Kovalchuk I., Abramov V, Pogribny I and Kovalchuk O. (2004) Molecular aspects of plant adaptation to life in the Chernobyl zone. Plant Physiology 135, 357-363.

•  Besplug J ., Filkowski J ., Burke P., Kovalchuk I. and O. Kovalchuk (2004) Atrazine induces homologous recombination but not point mutation in the transgenic plant-based biomonotoring assay. Archives of Environmental Contamination and Toxicology 46, 296-300.

•  Filkowski, J., Kovalchuk, O. and Kovalchuk, I. (2004) Genome stability of vtc1, tt4 and tt5 Arabidopsis thaliana mutants impaired in protection against oxidative stress. Plant Journal 38, 60-69.

•  Filkowski, J., Yeoman, A., Kovalchuk, O. and Kovalchuk, I. (2004) Systemic plant signal triggers genome instability. Plant Journal 38, 1-11.


•  Kovalchuk O ., Burke P., Arkhipov A., Kuchma N., James S. J., Kovalchuk I. and Pogribny I (2003) Genome hypermethylation Pinus silvestris of Chernobyl – a mechanisms for radiation adaptation? Mutation Research 529, 13-20.

•  Kovalchuk O., Kovalchuk, I, Arkhipov A. , Hohn B. and Y. Dubrova (2003) Extremely complex patterns of ionizing radiation-induced mutation in wheat microsatellite loci, Mutation Research 525, 93-101.

•  Kovalchuk, I. , Kovalchuk, O ., Kalck, V., Boyko, V., Filkowski, J., Heinlein, M. and Hohn, B. (2003) Pathogen induced systemic plant signal triggers DNA rearrangements. Nature 423, 760-762.

•  Kovalchuk O., Telyuk P., Kovalchuk I., Kovalchuk L. and V. Titov (2003) Plant bioassays for monitoring of the genotoxicity of drinking water from the inhabited areas of Ukraine affected by the Chernobyl accident. Bulletin of Environmental Contamination and Toxicology 70, 847-853.

•  Filkowski J ., Besplug J ., Burke P., Kovalchuk I. and O. Kovalchuk (2003) Recombination- and point mutation-monitoring transgenic plants reveal the genotoxicity of commonly used herbicides 2,4-D and dicamba. Mutation Research , 542, 23-32.

•  Kovalchuk, I. , Filkowski, J., Smith, K. and Kovalchuk, O. (2003) The dualistic nature of radicals: the high-low phenomenon. Plant Cell and Environment , 26, 1531-1539.

•  Kovalchuk I. and O. Kovalchuk (2003) A New Use for Transgenic Plants – Environmental Biomonitors. Biotechnol Genet Eng Rev. 20, 23-45 .


•  Kovalchuk O ., Hohn B., and I. Kovalchuk (2002) Transgenic plants for environmental biomonitoring: new perspectives. K. Vasil (ed.) Plant Biotechnology 2002 and Beyond . Kluwer Academic Publishers, 479-483.


•  Kovalchuk I. and Kovalchuk O. Biomonitoring with transgenic plants (2001) ISB News Report. Covering Agricultural and Environmental Biotechnnology Developments , September, 1-4.

•  Kovalchuk, I. , Kovalchuk, O. and B. Hohn (2001) Biomonitoring of genotoxicity of environmental factors with transgenic plants. Trends Plant Sci . 6 , 306- 3 10 .

•  Kovalchuk, O., Titov, V., Hohn, B. and I. Kovalchuk (2001) A sensitive transgenic plant system to detect toxic inorganic compounds in the environment. Nature Biotechnology, 19 , 568- 5 72 .


•  Frisch, O., Hohn B., Kovalchuk, I. et Kovalchuk O. (2000) Des bio-indicateurs de pollution radioactive , Biofutur 205, 48-51.

•  Kovalchuk O., Arkhipov A., Dubrova Yu., Hohn B. and Kovalchuk I. Wheat mutation rate after Chernobyl (2000) Nature 407, 583-584.

•  Kovalchuk I., Kovalchuk O., Hohn B. Genome-wide variation of the somatic mutation frequency in transgenic plants (2000) EMBO J , 19, 4431-4438.

•  Kovalchuk O., Arkhipov A., Barylyak I. , Karachov I. , Titov V., Hohn B. and I. Kovalchuk (2000) Plants experiencing chronic internal exposure to ionizing radiation exhibit higher frequency of homologous recombination than acutely irradiated plants. Mutation Research , 449, p.47-56.


•  Kovalchuk, O.; Kovalchuk, I. ; Titov, V.; Arkhipov, A. and Hohn, B. (1999) Radiation hazard caused by the Chernobyl accident in inhabited areas of Ukraine can be monitored by transgenic plants. Mutation Research 446, p.49-55.

•  Hohn B., Kovalchuk I. , Kovalchuk O . (1999) Transgenic plants sense radioactive contamination. Bioworld , 6, p. 13-15.

•  Kovalchuk I., Kovalchuk O. , Hohn B. (1999) Transgenic plants as bioindicators of environmental pollution. Review. AgBiotechNet, Vol. 1, October, ABN 030.


Kovalchuk I. , Kovalchuk O ., Arkhipov A., and Hohn B. (1998) Transgenic Plants Are Sensitive Bioindicators of Nuclear Pollution Caused by the Chernobyl Accident. Nature Biotechnology , 16, p.1054-1057.

•  Kovalchuk O ., Kovalchuk I. , Arkhipov A., Telyuk P., Hohn B., and L. Kovalchuk (1998) Allium cepa chromosome aberration test reliably measures genotoxicity of soils of inhabited areas of the Ukraine contaminated by the Chernobyl accident. Mutation Research , 415,1-2, p. 47-57.

Other refereed contributions:

•  Kovalchuk O ., Kovalchuk I. , and Hohn B. (1997) Estimation of the genotoxicity of soils using transgenic plants: new approach of carrying out environmental monitoring. Proceedings of international seminar: Environmental protection: New Trends in Microbiology and Ecology , Uzhorod , Ukraine , vol.2., p.13-16.

•  Kovalchuk O. (1997) Influence of ionizing radiation on the frequency of somatic homologous recombination in higher plants genome. Doctors' Journal of Galichina , 4(4), p.89-93 (In Ukrainian)

•  Kovalchuk O. (1998) Influence of soil radioactive contamination on the genome stability of higher eukarytes. Doctors' Journal of Galichina , 5(1), p.36-39 (In Ukrainian).

Edited books

“Epigenetics of genome instability and transgenerational effects” by Nova Science Publishers Inc. Co-editors – I. Kovalchuk and O. Kovalchuk . Pub. Date: 2010, 1st quarter.

Book chapters

Kovalchuk I. and Kovalchuk O . (2008) Monitoring heavy metal pollution with transgenic plants. In “Causes and Effects of Heavy Metal Pollution” by Nova Science Publishers Inc., pp. 287-303.

C. Yauk, A. Franck, A. Jha, O. Kovalchuk . (2010) DNA Fingerprinting Approaches for detection of DNA Mutation and Epigenetic Effects (in press).

J. Filkowski and O. Kovalchuk . (2010) Genetic and epigenetic mechanisms that safeguard genome stability of mammalian cells. In “Epigenetics of genome instability and transgenerational effects” by Nova Science Publishers Inc. (in press).

J. Filkowski, Y. Ilnytskyy and O. Kovalchuk (2010) Role of epigenetic dysregulation in radiation-induced genome instability and transgenerational effects. In “Epigenetics of genome instability and transgenerational effects” by Nova Science Publishers Inc. (in press).

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