No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.

Detalhes bibliográficos
Autor(a) principal: Camargo, Elaine Aparecida de
Data de Publicação: 2013
Outros Autores: Silva, Glenda Nicioli da, Gobette, Camila Pereira, Marcondes, João Paulo de Castro, Salvadori, Daisy Maria Fávero
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFOP
Texto Completo: http://www.repositorio.ufop.br/handle/123456789/5534
https://doi.org/10.7314/apjcp.2013.14.10.5941
Resumo: Tumor response to antineoplastic drugs is not always predictable. This is also true for bladder carcinoma, a highly recurrent neoplasia. Currently, the combination of cisplatin and gemcitabine is well accepted as a standard protocol for treating bladder carcinoma. However, in some cases, this treatment protocol causes harmful side effects. Therefore, we investigated the roles of the genes TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53 status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A and hMLH1 expression in the two cell lines. Increased DNA damage was observed in both cell lines after treatment with cisplatin or gemcitabine and with the two drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A expression and hypermethylation of its promoter were observed before and after treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated to methylation status, was observed in RT4 cells after treatment with cisplatin or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells, hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the three treatment protocols were genotoxic, independent of TP53 status. However, cisplatin was the most effective, causing the highest level of DNA damage in both wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in both cell lines. Furthermore, no relationship was observed between the amount of DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other alternative pathways might be involved in cisplatin and gemcitabine genotoxicity in these two bladder cancer cell lines.
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spelling No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.Gene expression profileGenotoxicityTumor response to antineoplastic drugs is not always predictable. This is also true for bladder carcinoma, a highly recurrent neoplasia. Currently, the combination of cisplatin and gemcitabine is well accepted as a standard protocol for treating bladder carcinoma. However, in some cases, this treatment protocol causes harmful side effects. Therefore, we investigated the roles of the genes TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53 status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A and hMLH1 expression in the two cell lines. Increased DNA damage was observed in both cell lines after treatment with cisplatin or gemcitabine and with the two drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A expression and hypermethylation of its promoter were observed before and after treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated to methylation status, was observed in RT4 cells after treatment with cisplatin or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells, hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the three treatment protocols were genotoxic, independent of TP53 status. However, cisplatin was the most effective, causing the highest level of DNA damage in both wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in both cell lines. Furthermore, no relationship was observed between the amount of DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other alternative pathways might be involved in cisplatin and gemcitabine genotoxicity in these two bladder cancer cell lines.2015-05-26T18:34:09Z2015-05-26T18:34:09Z2013info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfCAMARGO, E. A. de et al. No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine. Asian Pacific Journal of Cancer Prevention, v. 14, p. 5941-5948, 2013. Disponível em: <http://koreascience.or.kr/article/JAKO201305981337960.page>. Acesso em: 22 mai. 2015.1513-7368http://www.repositorio.ufop.br/handle/123456789/5534https://doi.org/10.7314/apjcp.2013.14.10.5941Papers published by APJCP are published and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/ licenses/by/3.0/), under which authors reserve the copyright for their content; however, they permit anyone unrestricted non-commercial use as long as the original authors and source are cited. Fonte: APJCP <http://www.apocpcontrol.org/page/information.php>. Acesso em: 22 maio 2015.info:eu-repo/semantics/openAccessCamargo, Elaine Aparecida deSilva, Glenda Nicioli daGobette, Camila PereiraMarcondes, João Paulo de CastroSalvadori, Daisy Maria Fáveroengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOP2019-07-26T17:20:39Zoai:repositorio.ufop.br:123456789/5534Repositório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332019-07-26T17:20:39Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false
dc.title.none.fl_str_mv No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.
title No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.
spellingShingle No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.
Camargo, Elaine Aparecida de
Gene expression profile
Genotoxicity
title_short No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.
title_full No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.
title_fullStr No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.
title_full_unstemmed No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.
title_sort No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine.
author Camargo, Elaine Aparecida de
author_facet Camargo, Elaine Aparecida de
Silva, Glenda Nicioli da
Gobette, Camila Pereira
Marcondes, João Paulo de Castro
Salvadori, Daisy Maria Fávero
author_role author
author2 Silva, Glenda Nicioli da
Gobette, Camila Pereira
Marcondes, João Paulo de Castro
Salvadori, Daisy Maria Fávero
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Camargo, Elaine Aparecida de
Silva, Glenda Nicioli da
Gobette, Camila Pereira
Marcondes, João Paulo de Castro
Salvadori, Daisy Maria Fávero
dc.subject.por.fl_str_mv Gene expression profile
Genotoxicity
topic Gene expression profile
Genotoxicity
description Tumor response to antineoplastic drugs is not always predictable. This is also true for bladder carcinoma, a highly recurrent neoplasia. Currently, the combination of cisplatin and gemcitabine is well accepted as a standard protocol for treating bladder carcinoma. However, in some cases, this treatment protocol causes harmful side effects. Therefore, we investigated the roles of the genes TP53, RASSF1A (a tumor suppressor gene) and hMLH1 (a gene involved in the mismatch repair pathway) in cell susceptibility to cisplatin/gemcitabine treatment. Two bladder transitional carcinoma cell (TCC) lines, RT4 (wild-type TP53) and 5637 (mutated TP53), were used in this study. First, we evaluated whether the genotoxic potential of cisplatin/gemcitabine was dependent on TP53 status. Then, we evaluated whether the two antineoplastic drugs modulated RASSF1A and hMLH1 expression in the two cell lines. Increased DNA damage was observed in both cell lines after treatment with cisplatin or gemcitabine and with the two drugs simultaneously, as depicted by the comet assay. A lack of RASSF1A expression and hypermethylation of its promoter were observed before and after treatment in both cell lines. On the other hand, hMLH1 downregulation, unrelated to methylation status, was observed in RT4 cells after treatment with cisplatin or with cisplatin and gemcitabine simultaneously (wild-type TP53); in 5637 cells, hMLH1 was upregulated only after treatment with gemcitabine. In conclusion, the three treatment protocols were genotoxic, independent of TP53 status. However, cisplatin was the most effective, causing the highest level of DNA damage in both wild-type and mutated TP53 cells. Gemcitabine was the least genotoxic agent in both cell lines. Furthermore, no relationship was observed between the amount of DNA damage and the level of hMLH1 and RASSF1A expression. Therefore, other alternative pathways might be involved in cisplatin and gemcitabine genotoxicity in these two bladder cancer cell lines.
publishDate 2013
dc.date.none.fl_str_mv 2013
2015-05-26T18:34:09Z
2015-05-26T18:34:09Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv CAMARGO, E. A. de et al. No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine. Asian Pacific Journal of Cancer Prevention, v. 14, p. 5941-5948, 2013. Disponível em: <http://koreascience.or.kr/article/JAKO201305981337960.page>. Acesso em: 22 mai. 2015.
1513-7368
http://www.repositorio.ufop.br/handle/123456789/5534
https://doi.org/10.7314/apjcp.2013.14.10.5941
identifier_str_mv CAMARGO, E. A. de et al. No relationship between the amount of DNA damage and the level of hMLH1 and RASSF1A gene expression in bladder cancer cells treated with cisplatin and gemcitabine. Asian Pacific Journal of Cancer Prevention, v. 14, p. 5941-5948, 2013. Disponível em: <http://koreascience.or.kr/article/JAKO201305981337960.page>. Acesso em: 22 mai. 2015.
1513-7368
url http://www.repositorio.ufop.br/handle/123456789/5534
https://doi.org/10.7314/apjcp.2013.14.10.5941
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFOP
instname:Universidade Federal de Ouro Preto (UFOP)
instacron:UFOP
instname_str Universidade Federal de Ouro Preto (UFOP)
instacron_str UFOP
institution UFOP
reponame_str Repositório Institucional da UFOP
collection Repositório Institucional da UFOP
repository.name.fl_str_mv Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)
repository.mail.fl_str_mv repositorio@ufop.edu.br
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