Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.mrgentox.2019.07.006 http://hdl.handle.net/11449/189448 |
Resumo: | Red and processed meat consumption has been strongly related to increase the risk of colorectal cancer (CRC), although its impact is largely unknown. Hemin, an iron-containing porphyrin, is acknowledged as a putative factor of red and processed meat pro-carcinogenic effects. The aim of this study was to investigate the effects of high dietary hemin on the promotion/progression stages of 1,2-dimethylhydrazine (1,2- DMH)-induced colon carcinogenesis. Twenty-four Wistar male rats were given four subcutaneous 1,2-DMH injections and received either balanced diet or balanced diet supplemented with hemin 0.5 mmol/kg for 23 weeks. Colon specimens were analyzed for aberrant crypt foci (ACF) and tumor development. Dietary hemin significantly increased ACF number and fecal water cytotoxicity/genotoxicity in Caco-2 cells when compared to 1,2-DMH control group. However, tumor incidence, multiplicity and cell proliferation did not differ between 1,2-DMH + hemin and 1,2-DMH control group. Gene expression analysis of 91 target-genes revealed that only three genes (Figf, Pik3r5 and Tgfbr2) were down-regulated in the tumors from hemin-fed rats compared to those from 1,2-DMH control group. Therefore, the findings of this study show that high hemin intake promotes mainly DNA damage and ACF development and but does not change the number nor incidence of colon tumors induced by 1,2-DMH in male rats. |
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Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats1,2-dimethylhydrazineAberrant crypt fociColorectal cancerDNA damageHeminRed and processed meat consumption has been strongly related to increase the risk of colorectal cancer (CRC), although its impact is largely unknown. Hemin, an iron-containing porphyrin, is acknowledged as a putative factor of red and processed meat pro-carcinogenic effects. The aim of this study was to investigate the effects of high dietary hemin on the promotion/progression stages of 1,2-dimethylhydrazine (1,2- DMH)-induced colon carcinogenesis. Twenty-four Wistar male rats were given four subcutaneous 1,2-DMH injections and received either balanced diet or balanced diet supplemented with hemin 0.5 mmol/kg for 23 weeks. Colon specimens were analyzed for aberrant crypt foci (ACF) and tumor development. Dietary hemin significantly increased ACF number and fecal water cytotoxicity/genotoxicity in Caco-2 cells when compared to 1,2-DMH control group. However, tumor incidence, multiplicity and cell proliferation did not differ between 1,2-DMH + hemin and 1,2-DMH control group. Gene expression analysis of 91 target-genes revealed that only three genes (Figf, Pik3r5 and Tgfbr2) were down-regulated in the tumors from hemin-fed rats compared to those from 1,2-DMH control group. Therefore, the findings of this study show that high hemin intake promotes mainly DNA damage and ACF development and but does not change the number nor incidence of colon tumors induced by 1,2-DMH in male rats.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Morphology Institute of Biosciences of Botucatu Sao Paulo State University (UNESP)Molecular Oncology Research Center Barretos Cancer HospitalBarretos School of Health Sciences, Dr. Paulo Prata - FACISBDepartment of Pathology School of Medicine Sao Paulo State University (UNESP)Department of Morphology Institute of Biosciences of Botucatu Sao Paulo State University (UNESP)Department of Pathology School of Medicine Sao Paulo State University (UNESP)Universidade Estadual Paulista (Unesp)Barretos Cancer HospitalBarretos School of Health Sciencesde Moura, Nelci A. [UNESP]Caetano, Brunno F.R. [UNESP]Bidinotto, Lucas T.Rodrigues, Maria A.M. [UNESP]Barbisan, Luis F. [UNESP]2019-10-06T16:41:02Z2019-10-06T16:41:02Z2019-01-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.mrgentox.2019.07.006Mutation Research - Genetic Toxicology and Environmental Mutagenesis.1879-35921383-5718http://hdl.handle.net/11449/18944810.1016/j.mrgentox.2019.07.0062-s2.0-85069699492Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengMutation Research - Genetic Toxicology and Environmental Mutagenesisinfo:eu-repo/semantics/openAccess2021-10-23T05:43:37Zoai:repositorio.unesp.br:11449/189448Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T05:43:37Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats |
title |
Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats |
spellingShingle |
Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats de Moura, Nelci A. [UNESP] 1,2-dimethylhydrazine Aberrant crypt foci Colorectal cancer DNA damage Hemin |
title_short |
Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats |
title_full |
Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats |
title_fullStr |
Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats |
title_full_unstemmed |
Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats |
title_sort |
Dietary hemin promotes colonic preneoplastic lesions and DNA damage but not tumor development in a medium-term model of colon carcinogenesis in rats |
author |
de Moura, Nelci A. [UNESP] |
author_facet |
de Moura, Nelci A. [UNESP] Caetano, Brunno F.R. [UNESP] Bidinotto, Lucas T. Rodrigues, Maria A.M. [UNESP] Barbisan, Luis F. [UNESP] |
author_role |
author |
author2 |
Caetano, Brunno F.R. [UNESP] Bidinotto, Lucas T. Rodrigues, Maria A.M. [UNESP] Barbisan, Luis F. [UNESP] |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Barretos Cancer Hospital Barretos School of Health Sciences |
dc.contributor.author.fl_str_mv |
de Moura, Nelci A. [UNESP] Caetano, Brunno F.R. [UNESP] Bidinotto, Lucas T. Rodrigues, Maria A.M. [UNESP] Barbisan, Luis F. [UNESP] |
dc.subject.por.fl_str_mv |
1,2-dimethylhydrazine Aberrant crypt foci Colorectal cancer DNA damage Hemin |
topic |
1,2-dimethylhydrazine Aberrant crypt foci Colorectal cancer DNA damage Hemin |
description |
Red and processed meat consumption has been strongly related to increase the risk of colorectal cancer (CRC), although its impact is largely unknown. Hemin, an iron-containing porphyrin, is acknowledged as a putative factor of red and processed meat pro-carcinogenic effects. The aim of this study was to investigate the effects of high dietary hemin on the promotion/progression stages of 1,2-dimethylhydrazine (1,2- DMH)-induced colon carcinogenesis. Twenty-four Wistar male rats were given four subcutaneous 1,2-DMH injections and received either balanced diet or balanced diet supplemented with hemin 0.5 mmol/kg for 23 weeks. Colon specimens were analyzed for aberrant crypt foci (ACF) and tumor development. Dietary hemin significantly increased ACF number and fecal water cytotoxicity/genotoxicity in Caco-2 cells when compared to 1,2-DMH control group. However, tumor incidence, multiplicity and cell proliferation did not differ between 1,2-DMH + hemin and 1,2-DMH control group. Gene expression analysis of 91 target-genes revealed that only three genes (Figf, Pik3r5 and Tgfbr2) were down-regulated in the tumors from hemin-fed rats compared to those from 1,2-DMH control group. Therefore, the findings of this study show that high hemin intake promotes mainly DNA damage and ACF development and but does not change the number nor incidence of colon tumors induced by 1,2-DMH in male rats. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-06T16:41:02Z 2019-10-06T16:41:02Z 2019-01-01 |
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/10.1016/j.mrgentox.2019.07.006 Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 1879-3592 1383-5718 http://hdl.handle.net/11449/189448 10.1016/j.mrgentox.2019.07.006 2-s2.0-85069699492 |
url |
http://dx.doi.org/10.1016/j.mrgentox.2019.07.006 http://hdl.handle.net/11449/189448 |
identifier_str_mv |
Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 1879-3592 1383-5718 10.1016/j.mrgentox.2019.07.006 2-s2.0-85069699492 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Mutation Research - Genetic Toxicology and Environmental Mutagenesis |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus 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 |
|
_version_ |
1799965379227811840 |