The effects of Co-exposure of tobacco smoke with Dibenzo[a,l]pyrene diol epoxide on molecular targets and immune cells in the mouse oral cavity.

IF 5.4
Chemico-biological interactions Pub Date : 2025-10-22 Epub Date: 2025-08-05 DOI:10.1016/j.cbi.2025.111694
Todd D Schell, Zachary T Bitzer, Kun-Ming Chen, Cesar Aliaga, Yuan-Wan Sun, Dhimant Desai, Matthew Lanza, Jiafen Hu, Neil Christensen, Karam El-Bayoumy
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Abstract

Tobacco smoking (TS) is an established etiological factor in the development of head and neck squamous cell carcinoma (HNSCC). We previously developed a mouse model using a select tobacco carcinogen, dibenzo[a,l]pyrene (DB[a,l]P, and its ultimate carcinogenic metabolite diol-epoxide (DB[a,l]PDE) to induce oral squamous cell carcinoma (OSCC) in mice; the molecular characteristics and histological changes observed in the mouse oral cavity mimic those found in human HNSCC. In the present study, using our mouse model, we examined for the first time the co-carcinogenic effects of TS with DB[a,l]PDE on DNA damage, histology, molecular targets, and immune cell regulation. We observed a non-significant increase of the levels of DB[a,l]PDE-DNA adduct in the oral cavity of mice exposed to TS as compared to those exposed to compressed air. Histologically, we observed significant increases in epithelial hyperplasia and epithelial single cell necrosis in TS treated mice. TS significantly enhanced protein expression of NF-κB and Ki67 while the enhancement of COX-2 did not reach significance but p53 expression was significantly decreased. We analyzed immune cell regulation in both spleen and tongue (target organ). No significant changes were observed in the spleen; however, in the tongue, we observed a significantly reduced frequency of CD3+T cells that included reductions of both CD4 and CD8 T cells and a corresponding increase was observed for multiple myeloid cell populations. While preliminary, our results offer the foundation for future research using this mouse model to explore the impact of co-carcinogens/tumor promotors other than TS on critical factors involved in the development of HNSCC.

烟草烟雾与二苯并[a, 1]芘二醇环氧化物共暴露对小鼠口腔分子靶点和免疫细胞的影响
吸烟(TS)是头颈部鳞状细胞癌(HNSCC)发展的一个确定的病因因素。我们之前建立了一个小鼠模型,使用烟草致癌物二苯并[a,l]芘(DB[a,l]P)及其最终致癌代谢物二醇环氧化物(DB[a,l]PDE)诱导小鼠口腔鳞状细胞癌(OSCC);在小鼠口腔中观察到的分子特征和组织学变化与人类HNSCC相似。在本研究中,我们利用小鼠模型首次检测了TS与DB[a,l]PDE在DNA损伤、组织学、分子靶点和免疫细胞调控方面的共同致癌作用。我们观察到,与暴露于压缩空气的小鼠相比,暴露于TS的小鼠口腔中DB[a,l]PDE-DNA加合物的水平没有显著增加。组织学上,我们观察到TS治疗小鼠上皮增生和上皮单细胞坏死显著增加。TS显著提高NF-κB和Ki67蛋白表达,COX-2蛋白表达增强不显著,但p53蛋白表达明显降低。我们分析了脾脏和舌(靶器官)的免疫细胞调节。脾脏未见明显变化;然而,在舌头中,我们观察到CD3+T细胞的频率显著降低,包括CD4和CD8T细胞的减少,并且在多发性骨髓细胞群中观察到相应的增加。虽然是初步的,但我们的结果为未来使用该小鼠模型探索除TS以外的共致癌物质/肿瘤促进因子对HNSCC发展关键因素的影响提供了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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