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 [UNESP]
Data de Publicação: 2013
Outros Autores: Silva, Glenda Nicioli da [UNESP], Gobette, Camila Pereira [UNESP], Castro Marcondes, Joao Paulo de [UNESP], Salvadori, Daisy Maria Favero [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.7314/APJCP.2013.14.10.5941
http://hdl.handle.net/11449/112300
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 GemcitabineDNA damageDNA repairgene 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.Sao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Botucatu, SP, BrazilUniv Fed Ouro Preto, Dept Anal Clin, Ouro Preto, BrazilSao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Botucatu, SP, BrazilAsian Pacific Organization Cancer PreventionUniversidade Estadual Paulista (Unesp)Universidade Federal de Ouro Preto (UFOP)Camargo, Elaine Aparecida de [UNESP]Silva, Glenda Nicioli da [UNESP]Gobette, Camila Pereira [UNESP]Castro Marcondes, Joao Paulo de [UNESP]Salvadori, Daisy Maria Favero [UNESP]2014-12-03T13:10:36Z2014-12-03T13:10:36Z2013-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5941-5948http://dx.doi.org/10.7314/APJCP.2013.14.10.5941Asian Pacific Journal Of Cancer Prevention. Gyeonggi-do: Asian Pacific Organization Cancer Prevention, v. 14, n. 10, p. 5941-5948, 2013.1513-7368http://hdl.handle.net/11449/11230010.7314/APJCP.2013.14.10.5941WOS:0003282742000625051118752980903Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengAsian Pacific Journal of Cancer Prevention0,616info:eu-repo/semantics/openAccess2024-09-03T13:18:13Zoai:repositorio.unesp.br:11449/112300Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:18:13Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)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 [UNESP]
DNA damage
DNA repair
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 [UNESP]
author_facet Camargo, Elaine Aparecida de [UNESP]
Silva, Glenda Nicioli da [UNESP]
Gobette, Camila Pereira [UNESP]
Castro Marcondes, Joao Paulo de [UNESP]
Salvadori, Daisy Maria Favero [UNESP]
author_role author
author2 Silva, Glenda Nicioli da [UNESP]
Gobette, Camila Pereira [UNESP]
Castro Marcondes, Joao Paulo de [UNESP]
Salvadori, Daisy Maria Favero [UNESP]
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Universidade Federal de Ouro Preto (UFOP)
dc.contributor.author.fl_str_mv Camargo, Elaine Aparecida de [UNESP]
Silva, Glenda Nicioli da [UNESP]
Gobette, Camila Pereira [UNESP]
Castro Marcondes, Joao Paulo de [UNESP]
Salvadori, Daisy Maria Favero [UNESP]
dc.subject.por.fl_str_mv DNA damage
DNA repair
gene expression profile
genotoxicity
topic DNA damage
DNA repair
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 2013-01-01
2014-12-03T13:10:36Z
2014-12-03T13:10:36Z
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 http://dx.doi.org/10.7314/APJCP.2013.14.10.5941
Asian Pacific Journal Of Cancer Prevention. Gyeonggi-do: Asian Pacific Organization Cancer Prevention, v. 14, n. 10, p. 5941-5948, 2013.
1513-7368
http://hdl.handle.net/11449/112300
10.7314/APJCP.2013.14.10.5941
WOS:000328274200062
5051118752980903
url http://dx.doi.org/10.7314/APJCP.2013.14.10.5941
http://hdl.handle.net/11449/112300
identifier_str_mv Asian Pacific Journal Of Cancer Prevention. Gyeonggi-do: Asian Pacific Organization Cancer Prevention, v. 14, n. 10, p. 5941-5948, 2013.
1513-7368
10.7314/APJCP.2013.14.10.5941
WOS:000328274200062
5051118752980903
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Asian Pacific Journal of Cancer Prevention
0,616
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 5941-5948
dc.publisher.none.fl_str_mv Asian Pacific Organization Cancer Prevention
publisher.none.fl_str_mv Asian Pacific Organization Cancer Prevention
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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