Tobacco smoke-induced squamous cell lung cancer develops from endobronchial dysplastic lesions that progress to invasive disease. A reproducible murine model recapitulating histologic progression observed in current and former smokers will advance testing of new preventive and therapeutic strategies. Previous studies show that prolonged topical application of N-nitroso-tris-chloroethylurea (NTCU) generates a range of airway lesions in sensitive mice similar to those induced by chronic tobacco smoke exposure in humans. To improve the current NTCU model and better align it with human disease, NTCU was applied to mice twice weekly for 4-5 weeks followed by a recovery period before cigarette smoke (CS) or ambient air (control) exposure for an additional 3-6 weeks. Despite the short time course, the addition of CS led to significantly more premalignant lesions (PML) (2.6 vs 0.5; p<0.02) and resulted in fewer alveolar macrophages (52,000 macrophages/ml BALF vs 68,000; p<0.05) compared to control mice. This improved NTCU + CS model is the first murine squamous cell lung cancer model to incorporate tobacco smoke and is more amenable to pre-clinical studies because of the increased number of PML, decreased number of mice required, and reduced time needed for PML development.

中文翻译：

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一种改进的小鼠癌前鳞状细胞模型：烟草烟雾暴露会增加 NTCU 诱导的小鼠气道发育不良

烟草烟雾诱发的鳞状细胞肺癌由支气管内发育不良病变发展为侵袭性疾病。一种可重现的小鼠模型，概括了在当前和以前的吸烟者中观察到的组织学进展，将推动对新的预防和治疗策略的测试。先前的研究表明，长期局部应用 N-亚硝基-三-氯乙基脲 (NTCU) 在敏感小鼠中会产生一系列气道损伤，类似于人类慢性烟草烟雾暴露引起的气道损伤。为了改进当前的 NTCU 模型并更好地使其与人类疾病保持一致，将 NTCU 每周两次应用于小鼠，持续 4-5 周，然后是在香烟烟雾 (CS) 或环境空气（对照）暴露之前的恢复期，额外 3-6周。尽管课程时间很短，与对照小鼠相比，添加 CS 导致癌前病变 (PML) 显着增加（2.6 对 0.5；p<0.02）并导致肺泡巨噬细胞减少（52,000 个巨噬细胞/ml BALF 对 68,000 个；p<0.05）。这种改进的 NTCU + CS 模型是第一个包含烟草烟雾的鼠鳞状细胞肺癌模型，并且由于 PML 数量增加、所需小鼠数量减少以及 PML 发育所需时间减少，因此更适合进行临床前研究。