Reiter Maximilian, Baumeister Philipp, Hartmann Martina, Schwenk-Zieger Sabina, Harréus Ulrich
Department of Otorhinolaryngology/Head and Neck Surgery, Grosshadern Clinic, Ludwig Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany.
In Vivo. 2014 Jan-Feb;28(1):49-53.
The head and neck region is one of the most important locations predisposed for tobacco-associated cancer. Chemoprevention might offer a chance to decrease the risk for this type of disease.
Mini-organ cultures (MOC) of macroscopically-healthy pharyngeal tissues from 20 patients with oropharyngeal squamous cell carcinoma (SCC) and from 20 controls were employed in the study. MOC were firstly incubated with Celecoxib, and DNA damage was induced by incubation with Benz[a]pyren-7,8-diol-9,10-epoxid (BPDE), a major representative of tobacco-associated carcinogens. DNA damage was evaluated with the alkaline single-cell microgel electrophoresis (Comet assay). Furthermore, fragmentation of the cyclin D1 gene, a gene of special importance in head and neck carcinogenesis was examined by the Comet-FISH assay. Finally, the chemoprotective potential of Celecoxib was analyzed after incubation with MOC.
As expected, BPDE caused significant DNA fragmentation in tumor compared to negative control tissues. No enhanced damage was observed in the cyclin D1 gene. DNA fragmentation was significantly reduced when MOC were incubated with Celecoxib in the tumor group. Surprisingly, these effects were also observed in the group without cancer of the oropharynx, although COX-2 is not expressed in macroscopically-healthy mucosa.
Celecoxib showed considerable chemoprotective effeciency against BPDE in both groups and this effect seems to be independent of COX-2 expression. No evidence for higher mutagen sensitivity in the Cyclin D1 gene was observed.
头颈部区域是与烟草相关癌症的最重要易患部位之一。化学预防可能为降低这类疾病的风险提供机会。
本研究采用了来自20例口咽鳞状细胞癌（SCC）患者和20例对照者的肉眼健康咽部组织的微型器官培养物（MOC）。首先将MOC与塞来昔布孵育，然后通过与苯并[a]芘-7,8-二醇-9,10-环氧化物（BPDE，一种与烟草相关致癌物的主要代表）孵育来诱导DNA损伤。用碱性单细胞微凝胶电泳（彗星试验）评估DNA损伤。此外，通过彗星荧光原位杂交试验检测细胞周期蛋白D1基因（在头颈部致癌过程中具有特殊重要性的一个基因）的片段化情况。最后，在与MOC孵育后分析塞来昔布的化学保护潜力。
正如预期的那样，与阴性对照组织相比，BPDE在肿瘤中引起了显著的DNA片段化。在细胞周期蛋白D1基因中未观察到增强的损伤。在肿瘤组中，当MOC与塞来昔布孵育时，DNA片段化显著减少。令人惊讶的是，在口咽无癌组中也观察到了这些效应，尽管COX-2在肉眼健康的黏膜中不表达。
塞来昔布在两组中均显示出对BPDE具有相当大的化学保护效率，并且这种效应似乎与COX-2表达无关。未观察到细胞周期蛋白D1基因中存在更高诱变敏感性的证据。
