Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France; Sorbonne Université, Department of Maxillo-Facial Surgery, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France.
Univ Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, Lyon, France.
Methods Cell Biol. 2021;163:197-229. doi: 10.1016/bs.mcb.2020.09.004. Epub 2020 Nov 12.
The early detection and management of oral premalignant lesions (OPMDs) improve their outcomes. Animal models that mimic histological and biological processes of human oral carcinogenesis may help to improve the identification of OPMD at-risk of progression into oral squamous cell carcinoma and to develop preventive strategies for the entire field of cancerization. No animal model is perfectly applicable for investigating human oral carcinogenesis. However, the 4-nitroquinoline 1-oxide (4-NQO) mouse model is well established and mimics several morphological, histological, genomic and molecular features of human oral carcinogenesis. Some of the reasons for the success of this model include its reproducible experimental conditions with limited variation, the possibility of realizing longitudinal studies with invasive intervention or gene manipulation, and sample availability for all stages of oral carcinogenesis, especially premalignant lesions. Moreover, the role of histological and molecular alterations in the field of cancerization (i.e., macroscopically healthy mucosa exposed to a carcinogen) during oral carcinogenesis can be easily explored using this model. In this review, we discuss the advantages and drawbacks of this model for studying human oral carcinogenesis. In summary, the 4-NQO-induced murine oral cancer model is relevant for investigating human oral carcinogenesis, including the immune microenvironment, and for evaluating therapeutic and chemoprevention agents.
早期发现和管理口腔癌前病变（OPMD）可以改善其预后。模拟人类口腔癌变的组织学和生物学过程的动物模型可能有助于提高对有进展为口腔鳞状细胞癌风险的 OPMD 的识别，并为整个癌变领域开发预防策略。没有一种动物模型完全适用于研究人类口腔癌变。然而，4-硝基喹啉 1-氧化物（4-NQO）小鼠模型已经建立，并且模拟了人类口腔癌变的几种形态、组织学、基因组和分子特征。该模型成功的原因之一是其具有可重复的实验条件，变异性有限，具有进行纵向研究和侵袭性干预或基因操作的可能性，并且可以获得所有口腔癌变阶段（尤其是癌前病变）的样本。此外，该模型还可以轻松探索癌变领域（即暴露于致癌物的宏观健康黏膜）中组织学和分子改变的作用。在这篇综述中，我们讨论了该模型在研究人类口腔癌变中的优缺点。综上所述，4-NQO 诱导的小鼠口腔癌模型与人类口腔癌变的研究有关，包括免疫微环境，以及评估治疗和化学预防剂的效果。
