Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium

Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are...
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Autor*in:	Liang Song [verfasserIn] Zizhi Tang [verfasserIn] Changsheng Peng [verfasserIn] Yueming Yang [verfasserIn] Chang Guo [verfasserIn] Danqing Wang [verfasserIn] Liandi Guo [verfasserIn] Jie Chen [verfasserIn] Cong Liu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Ovarian surface epithelium Steroid hormone DNA damage Homologous recombination

Übergeordnetes Werk:	In: BMC Cancer - BMC, 2003, 20(2020), 1, Seite 9
Übergeordnetes Werk:	volume:20 ; year:2020 ; number:1 ; pages:9

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1186/s12885-020-07524-7

Katalog-ID:	DOAJ003997219

Internformat


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520			\|a Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. Methods To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. Results We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. Conclusions Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively.
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allfields	10.1186/s12885-020-07524-7 doi (DE-627)DOAJ003997219 (DE-599)DOAJ71ecc41e1c8647deb2c317321a07b5da DE-627 ger DE-627 rakwb eng RC254-282 Liang Song verfasserin aut Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. Methods To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. Results We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. Conclusions Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively. Ovarian surface epithelium Steroid hormone DNA damage Homologous recombination Neoplasms. Tumors. Oncology. Including cancer and carcinogens Zizhi Tang verfasserin aut Changsheng Peng verfasserin aut Yueming Yang verfasserin aut Chang Guo verfasserin aut Danqing Wang verfasserin aut Liandi Guo verfasserin aut Jie Chen verfasserin aut Cong Liu verfasserin aut In BMC Cancer BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643710 (DE-600)2041352-X 14712407 nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/article/71ecc41e1c8647deb2c317321a07b5da kostenfrei http://link.springer.com/article/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/toc/1471-2407 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2020 1 9
spelling	10.1186/s12885-020-07524-7 doi (DE-627)DOAJ003997219 (DE-599)DOAJ71ecc41e1c8647deb2c317321a07b5da DE-627 ger DE-627 rakwb eng RC254-282 Liang Song verfasserin aut Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. Methods To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. Results We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. Conclusions Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively. Ovarian surface epithelium Steroid hormone DNA damage Homologous recombination Neoplasms. Tumors. Oncology. Including cancer and carcinogens Zizhi Tang verfasserin aut Changsheng Peng verfasserin aut Yueming Yang verfasserin aut Chang Guo verfasserin aut Danqing Wang verfasserin aut Liandi Guo verfasserin aut Jie Chen verfasserin aut Cong Liu verfasserin aut In BMC Cancer BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643710 (DE-600)2041352-X 14712407 nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/article/71ecc41e1c8647deb2c317321a07b5da kostenfrei http://link.springer.com/article/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/toc/1471-2407 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2020 1 9
allfields_unstemmed	10.1186/s12885-020-07524-7 doi (DE-627)DOAJ003997219 (DE-599)DOAJ71ecc41e1c8647deb2c317321a07b5da DE-627 ger DE-627 rakwb eng RC254-282 Liang Song verfasserin aut Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. Methods To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. Results We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. Conclusions Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively. Ovarian surface epithelium Steroid hormone DNA damage Homologous recombination Neoplasms. Tumors. Oncology. Including cancer and carcinogens Zizhi Tang verfasserin aut Changsheng Peng verfasserin aut Yueming Yang verfasserin aut Chang Guo verfasserin aut Danqing Wang verfasserin aut Liandi Guo verfasserin aut Jie Chen verfasserin aut Cong Liu verfasserin aut In BMC Cancer BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643710 (DE-600)2041352-X 14712407 nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/article/71ecc41e1c8647deb2c317321a07b5da kostenfrei http://link.springer.com/article/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/toc/1471-2407 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2020 1 9
allfieldsGer	10.1186/s12885-020-07524-7 doi (DE-627)DOAJ003997219 (DE-599)DOAJ71ecc41e1c8647deb2c317321a07b5da DE-627 ger DE-627 rakwb eng RC254-282 Liang Song verfasserin aut Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. Methods To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. Results We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. Conclusions Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively. Ovarian surface epithelium Steroid hormone DNA damage Homologous recombination Neoplasms. Tumors. Oncology. Including cancer and carcinogens Zizhi Tang verfasserin aut Changsheng Peng verfasserin aut Yueming Yang verfasserin aut Chang Guo verfasserin aut Danqing Wang verfasserin aut Liandi Guo verfasserin aut Jie Chen verfasserin aut Cong Liu verfasserin aut In BMC Cancer BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643710 (DE-600)2041352-X 14712407 nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/article/71ecc41e1c8647deb2c317321a07b5da kostenfrei http://link.springer.com/article/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/toc/1471-2407 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2020 1 9
allfieldsSound	10.1186/s12885-020-07524-7 doi (DE-627)DOAJ003997219 (DE-599)DOAJ71ecc41e1c8647deb2c317321a07b5da DE-627 ger DE-627 rakwb eng RC254-282 Liang Song verfasserin aut Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. Methods To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. Results We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. Conclusions Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively. Ovarian surface epithelium Steroid hormone DNA damage Homologous recombination Neoplasms. Tumors. Oncology. Including cancer and carcinogens Zizhi Tang verfasserin aut Changsheng Peng verfasserin aut Yueming Yang verfasserin aut Chang Guo verfasserin aut Danqing Wang verfasserin aut Liandi Guo verfasserin aut Jie Chen verfasserin aut Cong Liu verfasserin aut In BMC Cancer BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643710 (DE-600)2041352-X 14712407 nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/article/71ecc41e1c8647deb2c317321a07b5da kostenfrei http://link.springer.com/article/10.1186/s12885-020-07524-7 kostenfrei https://doaj.org/toc/1471-2407 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 20 2020 1 9
language	English
source	In BMC Cancer 20(2020), 1, Seite 9 volume:20 year:2020 number:1 pages:9
sourceStr	In BMC Cancer 20(2020), 1, Seite 9 volume:20 year:2020 number:1 pages:9
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Ovarian surface epithelium Steroid hormone DNA damage Homologous recombination Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	BMC Cancer
authorswithroles_txt_mv	Liang Song @@aut@@ Zizhi Tang @@aut@@ Changsheng Peng @@aut@@ Yueming Yang @@aut@@ Chang Guo @@aut@@ Danqing Wang @@aut@@ Liandi Guo @@aut@@ Jie Chen @@aut@@ Cong Liu @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	326643710
id	DOAJ003997219
language_de	englisch
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callnumber-first	R - Medicine
author	Liang Song
spellingShingle	Liang Song misc RC254-282 misc Ovarian surface epithelium misc Steroid hormone misc DNA damage misc Homologous recombination misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium
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topic_title	RC254-282 Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium Ovarian surface epithelium Steroid hormone DNA damage Homologous recombination
topic	misc RC254-282 misc Ovarian surface epithelium misc Steroid hormone misc DNA damage misc Homologous recombination misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc Ovarian surface epithelium misc Steroid hormone misc DNA damage misc Homologous recombination misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc Ovarian surface epithelium misc Steroid hormone misc DNA damage misc Homologous recombination misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium
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title_full	Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium
author_sort	Liang Song
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author_browse	Liang Song Zizhi Tang Changsheng Peng Yueming Yang Chang Guo Danqing Wang Liandi Guo Jie Chen Cong Liu
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title_sort	cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium
callnumber	RC254-282
title_auth	Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium
abstract	Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. Methods To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. Results We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. Conclusions Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively.
abstractGer	Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. Methods To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. Results We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. Conclusions Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively.
abstract_unstemmed	Abstract Background Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. Methods To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. Results We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. Conclusions Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively.
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container_issue	1
title_short	Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium
url	https://doi.org/10.1186/s12885-020-07524-7 https://doaj.org/article/71ecc41e1c8647deb2c317321a07b5da http://link.springer.com/article/10.1186/s12885-020-07524-7 https://doaj.org/toc/1471-2407
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up_date	2024-07-03T21:21:55.878Z
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Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium

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