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Diethylnitrosamine-Induced Liver Tumorigenesis in Mice Under High-Hat High-Sucrose Diet: Stepwise High-Resolution Ultrasound Imaging and Histopathological Correlations

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Liver Carcinogenesis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2769))

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Abstract

The hepatotoxic N-nitroso compound diethylnitrosamine (DEN) administered intraperitoneally (i.p.) induces liver neoplasms in rodents that reproducibly recapitulate some aspects of human hepatocarcinogenesis. In particular, DEN drives the stepwise formation of pre-neoplastic and neoplastic (benign or malignant) hepatocellular lesions reminiscent of the initiation-promotion-progression sequence typical of chemical carcinogenesis. In humans, the development of hepatocellular carcinoma (HCC) is also a multi-step process triggered by continuous hepatocellular injury, chronic inflammation, and compensatory hyperplasia that fuel the emergence of dysplastic liver lesions followed by the formation of early HCC. The DEN-induced liver tumorigenesis model represents a versatile preclinical tool that enables the study of many tumor development modifiers (genetic background, gene knockout or overexpression, diets, pollutants, or drugs) with a thorough follow-up of the multistage process on live animals by means of high-resolution imaging. Here, we provide a comprehensive protocol for the induction of hepatocellular neoplasms in wild-type C57BL/6J male mice following i.p. DEN injection (25 mg/kg) at 14 days of age and 36 weeks feeding of a high-fat high-sucrose (HFHS) diet. We emphasize the use of ultrasound liver imaging to follow tumor development and provide histopathological correlations. We also discuss the extrinsic and intrinsic factors known to modify the course of liver tumorigenesis in this model.

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Acknowledgments

The authors gratefully acknowledge the staff members from the animal core facility (Centre d’Exploration Fonctionnelle [CEF], Centre de Recherche des Cordeliers) and the histology core facilities (Centre d’Histologie, Imagerie et Cytométrie [CHIC], Centre de Recherche des Cordeliers and plateforme d’Histologie, Immunomarquage et Microdissection laser [HIST’IM], Institut Cochin). The authors also thank Dr. Vet. Med. Cécile Cazin for the helpful discussion and comments on the ultrasound examination of the normal and pathologic mouse liver.

The authors are supported by French grants from Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation pour la Recherche Médicale (Équipe FRM: EQU201903007824), Ligue Nationale Contre le Cancer (Equipe labellisée LNCC), Institut National du Cancer (PRTK-2017, PLBIO18-107), Agence Nationale de Recherche ANR (ANR-16-CE14; ANR-19-CE14-0044-01), Fondation ARC (Association de Recherche sur le Cancer), Ligue Contre le Cancer (comité de Paris), Cancéropôle Île-de-France (Emergence 2015), Association Française pour l’Étude du Foie (AFEF-SUBV 2017; AFEF-SUBV 2019), EVA-Plan Cancer INSERM HTE and SIRIC CARPEM. Dr. Vet. Med. P. Cordier is a recipient of Plan Cancer INSERM (“Soutien pour la formation à la recherche fondamentale et translationnelle en cancérologie” program). F. Sangouard is a recipient of Ministère de la Recherche funding (PhD grant). J. Fang is a recipient of Chinese Scholarship Council. P.C., F.S., and J.F. are members of Université Paris Cité IdEx #ANR-18-IDEX-0001 funded by the French Government through its “Investments for the Future” program.

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Author notes

  1. Pierre Cordier, Flora Sangouard and Jing Fang contributed equally.

Authors and Affiliations

  1. Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université Paris Cité, Paris, France

    Pierre Cordier, Flora Sangouard, Jing Fang, Christelle Kabore, Chantal Desdouets & Séverine Celton-Morizur

  2. Genomic Instability, Metabolism, Immunity and Liver Tumorigenesis Laboratory, Equipe Labellisée Ligue Contre le Cancer, Paris, France

    Pierre Cordier, Flora Sangouard, Jing Fang, Christelle Kabore, Chantal Desdouets & Séverine Celton-Morizur

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  1. Pierre Cordier
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  2. Flora Sangouard
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  4. Christelle Kabore
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  6. Séverine Celton-Morizur
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Correspondence to Séverine Celton-Morizur .

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Editors and Affiliations

  1. Centre de Recherche des Cordeliers, Paris, France

    Guido Kroemer

  2. Centre de Recherche des Cordeliers, Paris, France

    Jonathan Pol

  3. Centre de Recherche des Cordeliers, Paris, France

    Isabelle Martins

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Cordier, P., Sangouard, F., Fang, J., Kabore, C., Desdouets, C., Celton-Morizur, S. (2024). Diethylnitrosamine-Induced Liver Tumorigenesis in Mice Under High-Hat High-Sucrose Diet: Stepwise High-Resolution Ultrasound Imaging and Histopathological Correlations. In: Kroemer, G., Pol, J., Martins, I. (eds) Liver Carcinogenesis. Methods in Molecular Biology, vol 2769. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3694-7_3

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  • DOI: https://doi.org/10.1007/978-1-0716-3694-7_3

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-3693-0

  • Online ISBN: 978-1-0716-3694-7

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