Silver Nanoparticles Induced Changes in DNA Methylation and Histone H3 Methylation in a Mouse Model of Breast Cancer
The importance of epigenetic changes as a measurable endpoint in nanotoxicological studies is getting more and more appreciated. In the present work, we analyzed the epigenetic effects induced by citrate- and PEG-coated 20 nm silver nanoparticles (AgNPs) in a model consisting of 4T1 breast cancer tu...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
|
| Series: | Materials |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1996-1944/16/11/4163 |
| _version_ | 1797597128798765056 |
|---|---|
| author | Kamil Brzóska Barbara Sochanowicz Małgorzata Szczygieł Agnieszka Drzał Martyna Śniegocka Dominika Michalczyk-Wetula Martyna Elas Lucyna Kapka-Skrzypczak Marcin Kruszewski |
| author_facet | Kamil Brzóska Barbara Sochanowicz Małgorzata Szczygieł Agnieszka Drzał Martyna Śniegocka Dominika Michalczyk-Wetula Martyna Elas Lucyna Kapka-Skrzypczak Marcin Kruszewski |
| author_sort | Kamil Brzóska |
| collection | DOAJ |
| description | The importance of epigenetic changes as a measurable endpoint in nanotoxicological studies is getting more and more appreciated. In the present work, we analyzed the epigenetic effects induced by citrate- and PEG-coated 20 nm silver nanoparticles (AgNPs) in a model consisting of 4T1 breast cancer tumors in mice. Animals were administered with AgNPs intragastrically (1 mg/kg b.w. daily—total dose 14 mg/kg b.w.) or intravenously (administration twice with 1 mg/kg b.w.—total dose 2 mg/kg b.w.). We observed a significant decrease in 5-methylcytosine (5-mC) level in tumors from mice treated with citrate-coated AgNPs regardless of the route of administration. For PEG-coated AgNPs, a significant decrease in DNA methylation was observed only after intravenous administration. Moreover, treatment of 4T1 tumor-bearing mice with AgNPs decreased histone H3 methylation in tumor tissue. This effect was the most pronounced for PEG-coated AgNPs administered intravenously. No changes in histone H3 Lys9 acetylation were observed. The decrease in methylation of DNA and histone H3 was accompanied by changes in expression of genes encoding chromatin-modifying enzymes (Setd4, Setdb1, Smyd3, Suv39h1, Suv420h1, Whsc1, Kdm1a, Kdm5b, Esco2, Hat1, Myst3, Hdac5, Dnmt1, Ube2b, and Usp22) and genes related to carcinogenesis (Akt1, Brca1, Brca2, Mlh1, Myb, Ccnd1, and Src). The significance of the observed changes and the mechanisms responsible for their development are unclear, and more research in this area is warranted. Nevertheless, the present work points to the epigenetic effects as an important level of interaction between nanomaterials and biological systems, which should always be taken into consideration during analysis of the biological activity of nanomaterials and development of nanopharmaceuticals. |
| first_indexed | 2024-03-11T03:02:25Z |
| format | Article |
| id | doaj.art-2de4ff296e704e26ade337d0d743f503 |
| institution | Directory Open Access Journal |
| issn | 1996-1944 |
| language | English |
| last_indexed | 2024-03-11T03:02:25Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Materials |
| spelling | doaj.art-2de4ff296e704e26ade337d0d743f5032023-11-18T08:11:10ZengMDPI AGMaterials1996-19442023-06-011611416310.3390/ma16114163Silver Nanoparticles Induced Changes in DNA Methylation and Histone H3 Methylation in a Mouse Model of Breast CancerKamil Brzóska0Barbara Sochanowicz1Małgorzata Szczygieł2Agnieszka Drzał3Martyna Śniegocka4Dominika Michalczyk-Wetula5Martyna Elas6Lucyna Kapka-Skrzypczak7Marcin Kruszewski8Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, PolandCentre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, PolandDepartment of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, PolandDepartment of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, PolandDepartment of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, PolandDepartment of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, PolandDepartment of Biophysics and Cancer Biology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Cracow, PolandDepartment of Molecular Biology and Translational Research, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, PolandCentre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, PolandThe importance of epigenetic changes as a measurable endpoint in nanotoxicological studies is getting more and more appreciated. In the present work, we analyzed the epigenetic effects induced by citrate- and PEG-coated 20 nm silver nanoparticles (AgNPs) in a model consisting of 4T1 breast cancer tumors in mice. Animals were administered with AgNPs intragastrically (1 mg/kg b.w. daily—total dose 14 mg/kg b.w.) or intravenously (administration twice with 1 mg/kg b.w.—total dose 2 mg/kg b.w.). We observed a significant decrease in 5-methylcytosine (5-mC) level in tumors from mice treated with citrate-coated AgNPs regardless of the route of administration. For PEG-coated AgNPs, a significant decrease in DNA methylation was observed only after intravenous administration. Moreover, treatment of 4T1 tumor-bearing mice with AgNPs decreased histone H3 methylation in tumor tissue. This effect was the most pronounced for PEG-coated AgNPs administered intravenously. No changes in histone H3 Lys9 acetylation were observed. The decrease in methylation of DNA and histone H3 was accompanied by changes in expression of genes encoding chromatin-modifying enzymes (Setd4, Setdb1, Smyd3, Suv39h1, Suv420h1, Whsc1, Kdm1a, Kdm5b, Esco2, Hat1, Myst3, Hdac5, Dnmt1, Ube2b, and Usp22) and genes related to carcinogenesis (Akt1, Brca1, Brca2, Mlh1, Myb, Ccnd1, and Src). The significance of the observed changes and the mechanisms responsible for their development are unclear, and more research in this area is warranted. Nevertheless, the present work points to the epigenetic effects as an important level of interaction between nanomaterials and biological systems, which should always be taken into consideration during analysis of the biological activity of nanomaterials and development of nanopharmaceuticals.https://www.mdpi.com/1996-1944/16/11/4163silver nanoparticlesAgNPsDNA methylationhistone modificationsepigenetics |
| spellingShingle | Kamil Brzóska Barbara Sochanowicz Małgorzata Szczygieł Agnieszka Drzał Martyna Śniegocka Dominika Michalczyk-Wetula Martyna Elas Lucyna Kapka-Skrzypczak Marcin Kruszewski Silver Nanoparticles Induced Changes in DNA Methylation and Histone H3 Methylation in a Mouse Model of Breast Cancer Materials silver nanoparticles AgNPs DNA methylation histone modifications epigenetics |
| title | Silver Nanoparticles Induced Changes in DNA Methylation and Histone H3 Methylation in a Mouse Model of Breast Cancer |
| title_full | Silver Nanoparticles Induced Changes in DNA Methylation and Histone H3 Methylation in a Mouse Model of Breast Cancer |
| title_fullStr | Silver Nanoparticles Induced Changes in DNA Methylation and Histone H3 Methylation in a Mouse Model of Breast Cancer |
| title_full_unstemmed | Silver Nanoparticles Induced Changes in DNA Methylation and Histone H3 Methylation in a Mouse Model of Breast Cancer |
| title_short | Silver Nanoparticles Induced Changes in DNA Methylation and Histone H3 Methylation in a Mouse Model of Breast Cancer |
| title_sort | silver nanoparticles induced changes in dna methylation and histone h3 methylation in a mouse model of breast cancer |
| topic | silver nanoparticles AgNPs DNA methylation histone modifications epigenetics |
| url | https://www.mdpi.com/1996-1944/16/11/4163 |
| work_keys_str_mv | AT kamilbrzoska silvernanoparticlesinducedchangesindnamethylationandhistoneh3methylationinamousemodelofbreastcancer AT barbarasochanowicz silvernanoparticlesinducedchangesindnamethylationandhistoneh3methylationinamousemodelofbreastcancer AT małgorzataszczygieł silvernanoparticlesinducedchangesindnamethylationandhistoneh3methylationinamousemodelofbreastcancer AT agnieszkadrzał silvernanoparticlesinducedchangesindnamethylationandhistoneh3methylationinamousemodelofbreastcancer AT martynasniegocka silvernanoparticlesinducedchangesindnamethylationandhistoneh3methylationinamousemodelofbreastcancer AT dominikamichalczykwetula silvernanoparticlesinducedchangesindnamethylationandhistoneh3methylationinamousemodelofbreastcancer AT martynaelas silvernanoparticlesinducedchangesindnamethylationandhistoneh3methylationinamousemodelofbreastcancer AT lucynakapkaskrzypczak silvernanoparticlesinducedchangesindnamethylationandhistoneh3methylationinamousemodelofbreastcancer AT marcinkruszewski silvernanoparticlesinducedchangesindnamethylationandhistoneh3methylationinamousemodelofbreastcancer |