Background/Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral cancer, progressing from hyperplasia to dysplasia, carcinoma in situ (CIS), and finally invasive squamous cell carcinoma (ISCC). Developing an animal model that mimics both early and advanced OSCC stages has been challenging. The 4-Nitroquinoline 1-oxide (4NQO) model is considered one of the most suitable, as it represents all stages of OSCC. Nevertheless, thoroughly understanding the properties of the 4NQO model is essential for preclinical testing of novel therapeutics. Methods: We aimed to characterize the 4NQO rat model using two application methods—drinking water and topical application—over eight months. Monthly sacrifices allowed histopathological analysis and ex vivo magnetic resonance imaging (MRI) to track tumor progression. Results: CIS was observed at three months in the drinking water group, evolving into ISCC by six months, while topical application induced CIS at eight months without ISCC formation. The tongue was divided into three regions and histological properties, lesion size, and invasion depth were analyzed. In the drinking water group, particularly in the body of the tongue, we saw earlier CIS development, larger lesions, and deeper invasion. Additionally, assessment of proliferative properties showed an increased cell division in dysplastic lesions that reduced upon invasion. MRI was able to show macroscopic tumoral lesions, in concordance with histology. Conclusions: Overall, the drinking water method closely mimics human OSCC, validating the 4NQO model for translational OSCC research.
背景/目的：口腔鳞状细胞癌（OSCC）是最常见的口腔恶性肿瘤，其发展过程通常经历从增生、异常增生、原位癌（CIS）直至最终进展为浸润性鳞状细胞癌（ISCC）的病理阶段。建立能够同时模拟早期和晚期OSCC阶段的动物模型一直面临挑战。4-硝基喹啉-1-氧化物（4NQO）诱导模型因其能再现OSCC全病程进展，被认为是最适宜的模型之一。然而，深入理解该模型的特性对于新型治疗方法的临床前测试至关重要。方法：本研究通过饮用水给药与局部涂抹两种给药方式，在八个月周期内系统表征4NQO大鼠模型。通过每月处死动物进行组织病理学分析和离体磁共振成像（MRI），追踪肿瘤进展轨迹。结果：饮用水给药组在三个月时即观察到CIS病变，至六个月时进展为ISCC；而局部涂抹组在八个月时仅诱导出CIS，未形成ISCC。研究将舌体划分为三个区域进行分析，结果显示饮用水给药组（特别是舌体部）呈现更早的CIS发生时间、更大的病灶体积及更深的浸润深度。增殖特性评估显示异常增生病变中细胞分裂活动增强，而在浸润阶段有所减弱。MRI检测结果与组织病理学表现高度一致，能够清晰显示宏观肿瘤病灶。结论：综合而言，饮用水给药法能更精准地模拟人类OSCC进展特征，这验证了4NQO模型在转化性OSCC研究中的应用价值。
肿瘤(癌症)患者之家