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Article

Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats

by
Jaime Sánchez-Meza
1,
Marina Campos-Valdez
1,
José Alfredo Domínguez-Rosales
1,
Juliana Marisol Godínez-Rubí
2,
Sarai Citlalic Rodríguez-Reyes
3,
Erika Martínez-López
3,
Guillermo M. Zúñiga-González
4 and
Laura Verónica Sánchez-Orozco
1,*
1
Instituto de Enfermedades Crónico Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico
2
Laboratorio de Patología Diagnóstica e Inmunohistoquímica, Departamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Mexico
3
Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Guadalajara 44340, Mexico
4
Laboratorio de Mutagénesis, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara 44340, Mexico
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(9), 8387; https://doi.org/10.3390/ijms24098387
Submission received: 24 March 2023 / Revised: 30 April 2023 / Accepted: 5 May 2023 / Published: 7 May 2023
(This article belongs to the Section Molecular Biology)
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Abstract

This study aimed to analyze the biochemical, histological, and gene expression alterations produced in a hepatocarcinogenesis model induced by the chronic administration of diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) in Wistar rats. Thirteen rats weighing 180 to 200 g were divided into two groups: control and treated. Rats in the treated group were administered an intraperitoneal (i.p.) injection of DEN (50 mg/kg/week) and an intragastric (i.g.) dose of 2-AAF (25 mg/kg/week) for 18 weeks. The treated group had significant increases in their total cholesterol, HDL-C, AST, ALT, ALKP, and GGT levels. Furthermore, a histological analysis showed the loss of normal liver architecture with nuclear pleomorphism in the hepatocytes, atypical mitosis, and fibrous septa that were distributed between the portal triads and collagen fibers through the hepatic sinusoids. The gene expressions of 24 genes related to fibrosis, inflammation, apoptosis, cell growth, angiogenesis, lipid metabolism, and alpha-fetoprotein (AFP) were analyzed; only TGFβ, COL1α1, CYP2E1, CAT, SOD, IL6, TNF-α, and ALB showed significant differences when both groups were compared. Additionally, lung histopathological alterations were found in the treated group, suggesting metastasis. In this model, the chronic administration of DEN+2-AAF induces characteristic alterations of hepatocellular carcinoma in Wistar rats without AFP gene expression changes, highlighting different signatures in hepatocellular carcinoma heterogeneity.
Keywords: diethylnitrosamine; 2-acetylaminofluorene; hepatocellular carcinoma; Wistar rats; TGF-β; alpha-fetoprotein diethylnitrosamine; 2-acetylaminofluorene; hepatocellular carcinoma; Wistar rats; TGF-β; alpha-fetoprotein

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MDPI and ACS Style

Sánchez-Meza, J.; Campos-Valdez, M.; Domínguez-Rosales, J.A.; Godínez-Rubí, J.M.; Rodríguez-Reyes, S.C.; Martínez-López, E.; Zúñiga-González, G.M.; Sánchez-Orozco, L.V. Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats. Int. J. Mol. Sci. 2023, 24, 8387. https://doi.org/10.3390/ijms24098387

AMA Style

Sánchez-Meza J, Campos-Valdez M, Domínguez-Rosales JA, Godínez-Rubí JM, Rodríguez-Reyes SC, Martínez-López E, Zúñiga-González GM, Sánchez-Orozco LV. Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats. International Journal of Molecular Sciences. 2023; 24(9):8387. https://doi.org/10.3390/ijms24098387

Chicago/Turabian Style

Sánchez-Meza, Jaime, Marina Campos-Valdez, José Alfredo Domínguez-Rosales, Juliana Marisol Godínez-Rubí, Sarai Citlalic Rodríguez-Reyes, Erika Martínez-López, Guillermo M. Zúñiga-González, and Laura Verónica Sánchez-Orozco. 2023. "Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats" International Journal of Molecular Sciences 24, no. 9: 8387. https://doi.org/10.3390/ijms24098387

APA Style

Sánchez-Meza, J., Campos-Valdez, M., Domínguez-Rosales, J. A., Godínez-Rubí, J. M., Rodríguez-Reyes, S. C., Martínez-López, E., Zúñiga-González, G. M., & Sánchez-Orozco, L. V. (2023). Chronic Administration of Diethylnitrosamine and 2-Acetylaminofluorene Induces Hepatocellular Carcinoma in Wistar Rats. International Journal of Molecular Sciences, 24(9), 8387. https://doi.org/10.3390/ijms24098387

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