Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association

Background: Chronic injury deregulates cellular homeostasis and induces a number of alterations leading to disruption of cellular processes such as cell cycle checkpoints and apoptosis, driving to carcinogenesis. The stress protein heme oxygenase-1 (HO-1) catalyzes heme degradation producing biliver...

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Autores principales:	Castronuovo, Cynthia Celeste, Sacca, Paula Alejandra, Batlle, Alcira María del Carmen, Vázquez, Elba Susana
Publicado:	2006
Materias:	4 dimethylaminoazobenzene carcinogen cell cycle protein cyclin dependent kinase 2 cyclin dependent kinase inhibitor 1 cyclin E heme oxygenase 1 protein bcl 2 animal cell animal experiment animal model animal tissue article cell type cellular distribution controlled study dietary intake enzyme analysis hepatitis homeostasis immunohistochemistry in vivo study liver cell carcinoma liver necrosis liver regeneration macrophage male mouse mouse strain nonhuman oxidative stress protein expression protein induction Western blotting Animals Carcinogens Carcinoma, Hepatocellular Cell Cycle Cell Cycle Proteins Drug Administration Schedule Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Heme Oxygenase-1 Homeostasis Liver Neoplasms Male Mice Mice, Inbred Strains p-Dimethylaminoazobenzene
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14712407_v6_n_p_Castronuovo http://hdl.handle.net/20.500.12110/paper_14712407_v6_n_p_Castronuovo
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_14712407_v6_n_p_Castronuovo2023-06-08T16:17:20Z Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association Castronuovo, Cynthia Celeste Sacca, Paula Alejandra Batlle, Alcira María del Carmen Vázquez, Elba Susana 4 dimethylaminoazobenzene carcinogen cell cycle protein cyclin dependent kinase 2 cyclin dependent kinase inhibitor 1 cyclin E heme oxygenase 1 protein bcl 2 animal cell animal experiment animal model animal tissue article cell type cellular distribution controlled study dietary intake enzyme analysis hepatitis homeostasis immunohistochemistry in vivo study liver cell carcinoma liver necrosis liver regeneration macrophage male mouse mouse strain nonhuman oxidative stress protein expression protein induction Western blotting Animals Carcinogens Carcinoma, Hepatocellular Cell Cycle Cell Cycle Proteins Drug Administration Schedule Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Heme Oxygenase-1 Homeostasis Liver Neoplasms Male Mice Mice, Inbred Strains p-Dimethylaminoazobenzene Background: Chronic injury deregulates cellular homeostasis and induces a number of alterations leading to disruption of cellular processes such as cell cycle checkpoints and apoptosis, driving to carcinogenesis. The stress protein heme oxygenase-1 (HO-1) catalyzes heme degradation producing biliverdin, iron and CO. Induction of HO-1 has been suggested to be essential for a controlled cell growth. The aim of this work was to analyze the in vivo homeostatic response (HR) triggered by the withdrawal of a potent carcinogen, p-dimethylaminoazobenzene (DAB), after preneoplastic lesions were observed. We analyzed HO-1 cellular localization and the expression of HO-1, Bcl-2 and cell cycle related proteins under these conditions comparing them to hepatocellular carcinoma (HC). Methods: The intoxication protocol was designed based on previous studies demonstrating that preneoplastic lesions were evident after 89 days of chemical carcinogen administration. Male CF1 mice (n = 18) were used. HR group received DAB (0.5 % w/w) in the diet for 78 days followed by 11 days of carcinogen deprivation. The HC group received the carcinogen and control animals the standard diet during 89 days. The expression of cell cycle related proteins, of Bcl-2 and of HO-1 were analyzed by western blot. The cellular localization and expression of HO-1 were detected by immnunohistochemistry. Results: Increased expression of cyclin E/CDK2 was observed in HR, thus implicating cyclin E/CDK2 in the liver regenerative process. p21cip1/waf1 and Bcl-2 induction in HC was restituted to basal levels in HR. A similar response profile was found for HO-1 expression levels, showing a lower oxidative status in the carcinogen-deprived liver. The immunohistochemical studies revealed the presence of macrophages surrounding foci of necrosis and nodular lesions in HR indicative of an inflammatory response. Furthermore, regenerative cells displayed changes in type, size and intensity of HO-1 immunostaining. Conclusion: These results demonstrate that the regenera tive capacity of the liver is still observed in the pre-neoplastic tissue after carcinogen withdrawal suggesting that reversible mechanism/s to compensate necrosis and to restitute homeostasis are involved. © 2006 Castronuovo et al; licensee BioMed Central Ltd. Fil:Castronuovo, C.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Sacca, P.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Vazquez, E.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14712407_v6_n_p_Castronuovo http://hdl.handle.net/20.500.12110/paper_14712407_v6_n_p_Castronuovo
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	4 dimethylaminoazobenzene carcinogen cell cycle protein cyclin dependent kinase 2 cyclin dependent kinase inhibitor 1 cyclin E heme oxygenase 1 protein bcl 2 animal cell animal experiment animal model animal tissue article cell type cellular distribution controlled study dietary intake enzyme analysis hepatitis homeostasis immunohistochemistry in vivo study liver cell carcinoma liver necrosis liver regeneration macrophage male mouse mouse strain nonhuman oxidative stress protein expression protein induction Western blotting Animals Carcinogens Carcinoma, Hepatocellular Cell Cycle Cell Cycle Proteins Drug Administration Schedule Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Heme Oxygenase-1 Homeostasis Liver Neoplasms Male Mice Mice, Inbred Strains p-Dimethylaminoazobenzene
spellingShingle	4 dimethylaminoazobenzene carcinogen cell cycle protein cyclin dependent kinase 2 cyclin dependent kinase inhibitor 1 cyclin E heme oxygenase 1 protein bcl 2 animal cell animal experiment animal model animal tissue article cell type cellular distribution controlled study dietary intake enzyme analysis hepatitis homeostasis immunohistochemistry in vivo study liver cell carcinoma liver necrosis liver regeneration macrophage male mouse mouse strain nonhuman oxidative stress protein expression protein induction Western blotting Animals Carcinogens Carcinoma, Hepatocellular Cell Cycle Cell Cycle Proteins Drug Administration Schedule Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Heme Oxygenase-1 Homeostasis Liver Neoplasms Male Mice Mice, Inbred Strains p-Dimethylaminoazobenzene Castronuovo, Cynthia Celeste Sacca, Paula Alejandra Batlle, Alcira María del Carmen Vázquez, Elba Susana Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association
topic_facet	4 dimethylaminoazobenzene carcinogen cell cycle protein cyclin dependent kinase 2 cyclin dependent kinase inhibitor 1 cyclin E heme oxygenase 1 protein bcl 2 animal cell animal experiment animal model animal tissue article cell type cellular distribution controlled study dietary intake enzyme analysis hepatitis homeostasis immunohistochemistry in vivo study liver cell carcinoma liver necrosis liver regeneration macrophage male mouse mouse strain nonhuman oxidative stress protein expression protein induction Western blotting Animals Carcinogens Carcinoma, Hepatocellular Cell Cycle Cell Cycle Proteins Drug Administration Schedule Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Heme Oxygenase-1 Homeostasis Liver Neoplasms Male Mice Mice, Inbred Strains p-Dimethylaminoazobenzene
description	Background: Chronic injury deregulates cellular homeostasis and induces a number of alterations leading to disruption of cellular processes such as cell cycle checkpoints and apoptosis, driving to carcinogenesis. The stress protein heme oxygenase-1 (HO-1) catalyzes heme degradation producing biliverdin, iron and CO. Induction of HO-1 has been suggested to be essential for a controlled cell growth. The aim of this work was to analyze the in vivo homeostatic response (HR) triggered by the withdrawal of a potent carcinogen, p-dimethylaminoazobenzene (DAB), after preneoplastic lesions were observed. We analyzed HO-1 cellular localization and the expression of HO-1, Bcl-2 and cell cycle related proteins under these conditions comparing them to hepatocellular carcinoma (HC). Methods: The intoxication protocol was designed based on previous studies demonstrating that preneoplastic lesions were evident after 89 days of chemical carcinogen administration. Male CF1 mice (n = 18) were used. HR group received DAB (0.5 % w/w) in the diet for 78 days followed by 11 days of carcinogen deprivation. The HC group received the carcinogen and control animals the standard diet during 89 days. The expression of cell cycle related proteins, of Bcl-2 and of HO-1 were analyzed by western blot. The cellular localization and expression of HO-1 were detected by immnunohistochemistry. Results: Increased expression of cyclin E/CDK2 was observed in HR, thus implicating cyclin E/CDK2 in the liver regenerative process. p21cip1/waf1 and Bcl-2 induction in HC was restituted to basal levels in HR. A similar response profile was found for HO-1 expression levels, showing a lower oxidative status in the carcinogen-deprived liver. The immunohistochemical studies revealed the presence of macrophages surrounding foci of necrosis and nodular lesions in HR indicative of an inflammatory response. Furthermore, regenerative cells displayed changes in type, size and intensity of HO-1 immunostaining. Conclusion: These results demonstrate that the regenera tive capacity of the liver is still observed in the pre-neoplastic tissue after carcinogen withdrawal suggesting that reversible mechanism/s to compensate necrosis and to restitute homeostasis are involved. © 2006 Castronuovo et al; licensee BioMed Central Ltd.
author	Castronuovo, Cynthia Celeste Sacca, Paula Alejandra Batlle, Alcira María del Carmen Vázquez, Elba Susana
author_facet	Castronuovo, Cynthia Celeste Sacca, Paula Alejandra Batlle, Alcira María del Carmen Vázquez, Elba Susana
author_sort	Castronuovo, Cynthia Celeste
title	Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association
title_short	Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association
title_full	Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association
title_fullStr	Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association
title_full_unstemmed	Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association
title_sort	homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association
publishDate	2006
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14712407_v6_n_p_Castronuovo http://hdl.handle.net/20.500.12110/paper_14712407_v6_n_p_Castronuovo
work_keys_str_mv	AT castronuovocynthiaceleste homeostaticresponseundercarcinogenwithdrawalhemeoxygenase1expressionandcellcycleassociation AT saccapaulaalejandra homeostaticresponseundercarcinogenwithdrawalhemeoxygenase1expressionandcellcycleassociation AT batllealciramariadelcarmen homeostaticresponseundercarcinogenwithdrawalhemeoxygenase1expressionandcellcycleassociation AT vazquezelbasusana homeostaticresponseundercarcinogenwithdrawalhemeoxygenase1expressionandcellcycleassociation
_version_	1768546318068744192

Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association

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