Abstract:
Heme oxygenase (HO) breaks down the pro-oxidant heme into carbon monoxide, iron and the antioxidant biliverdin. The isoform HO-1 plays an effective role to counteract oxidative damage and to control inflammation. Prolonged cellular damage due to chronic inflammation is one of the reasons leading to the development of tumours. The aim of this work was to investigate HO-1 expression and localization along the different stages of chemically induced hepatocarcinogenesis (HCC) and the occurring morphological changes. To provoke sustained oxidative stress and chronic inflammation, CF1 mice received dietary p-dimethylaminoazobenzene (DAB, 0.5%, w/w) during a whole period of 14 months. HO-1 expression increased along the experimental trial in morphologically normal hepatocytes in DAB-treated animals. HO-1 expression diminished in altered hepatic foci (AHF) and oval cells and early preneoplastic lesions. Otherwise, marked HO-1 overexpression was detected in Kupffer cells and macrophages surrounding necrotic and nodular areas. Adenomas showed decreased HO-1 immunostaining. In hepatocellular carcinomas, an inverse relationship was found between the immunohistochemical expression of HO-1 and the degree of tumour differentiation, being negative in poorly differentiated tumours. In our experimental model, down modulation of HO-1 expression correlated with malignancy progression. Thus, our data point to activation of HO-1 as a potential therapeutic tool.
Registro:
Documento: |
Artículo
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Título: | Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis |
Autor: | Caballero, F.; Meiss, R.; Gimenez, A.; Batlle, A.; Vazquez, E. |
Filiación: | Ctro. Invest. Sobre Porfirinas P., Depto. de Quim. Biologica, UBA - Ciudad Universitaria, Buenos Aires, Argentina Departamento de Patología, Inst. de Estudios Oncológicos, Academia Nacional de Medicina, Buenos Aires, Argentina Viamonte 1881 100 A, 1056 - Buenos Aires, Argentina
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Palabras clave: | Heme oxygenase; Hepatocarcinogenesis; Inflammation; Oxidative stress; p-dimethylaminoazobenzene; 4 dimethylaminoazobenzene; antioxidant; biliverdin; carbon dioxide; heme oxygenase 1; iron; animal cell; animal experiment; animal tissue; article; cell damage; cell proliferation; chemical carcinogenesis; chronic inflammation; controlled study; disease course; enzyme localization; epithelium cell; immunohistochemistry; inflammation; Kupffer cell; liver adenoma; liver carcinogenesis; liver cell; liver cell carcinoma; liver injury; liver necrosis; macrophage; male; morphological trait; mouse strain; neoplasm; nonhuman; oxidation; oxidative stress; priority journal; protein expression; rat; tumor differentiation; Western blotting; Adenoma; Animals; Blotting, Western; Carcinoma, Hepatocellular; Disease Progression; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Hepatocytes; Immunoenzyme Techniques; Liver; Liver Neoplasms; Macrophages; Male; Membrane Proteins; Mice; Mice, Inbred Strains; Necrosis; p-Dimethylaminoazobenzene; Precancerous Conditions |
Año: | 2004
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Volumen: | 85
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Número: | 4
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Página de inicio: | 213
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Página de fin: | 221
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DOI: |
http://dx.doi.org/10.1111/j.0959-9673.2004.00391.x |
Título revista: | International Journal of Experimental Pathology
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Título revista abreviado: | Int. J. Exp. Pathol.
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ISSN: | 09599673
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CODEN: | IJEPE
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CAS: | 4 dimethylaminoazobenzene, 60-11-7; biliverdin, 114-25-0; carbon dioxide, 124-38-9, 58561-67-4; iron, 14093-02-8, 53858-86-9, 7439-89-6; Heme Oxygenase (Decyclizing), EC 1.14.99.3; Heme Oxygenase-1, EC 1.14.99.3; Hmox1 protein, mouse, EC 1.14.99.3; Membrane Proteins; p-Dimethylaminoazobenzene, 60-11-7
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09599673_v85_n4_p213_Caballero |
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Citas:
---------- APA ----------
Caballero, F., Meiss, R., Gimenez, A., Batlle, A. & Vazquez, E.
(2004)
. Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis. International Journal of Experimental Pathology, 85(4), 213-221.
http://dx.doi.org/10.1111/j.0959-9673.2004.00391.x---------- CHICAGO ----------
Caballero, F., Meiss, R., Gimenez, A., Batlle, A., Vazquez, E.
"Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis"
. International Journal of Experimental Pathology 85, no. 4
(2004) : 213-221.
http://dx.doi.org/10.1111/j.0959-9673.2004.00391.x---------- MLA ----------
Caballero, F., Meiss, R., Gimenez, A., Batlle, A., Vazquez, E.
"Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis"
. International Journal of Experimental Pathology, vol. 85, no. 4, 2004, pp. 213-221.
http://dx.doi.org/10.1111/j.0959-9673.2004.00391.x---------- VANCOUVER ----------
Caballero, F., Meiss, R., Gimenez, A., Batlle, A., Vazquez, E. Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis. Int. J. Exp. Pathol. 2004;85(4):213-221.
http://dx.doi.org/10.1111/j.0959-9673.2004.00391.x