Schwartz J L, West K, Shklar D P, Shklar G
Oral Disease and Prevention Program, National Institute of Dental Research, Bethesda, MD 20892, USA.
Nutr Cancer. 1995;24(1):47-56. doi: 10.1080/01635589509514392.
Epidermoid carcinomas were induced in hamster buccal pouches with use of 7.12 dimethylbenz[a]anthracene (DMBA). In five animals that served as tumor controls (Group 1), right buccal pouches were painted with DMBA (0.5% solution in mineral oil) thrice weekly for 14 weeks. In five animals (Group 2), right buccal pouches were painted with DMBA and reduced glutathione (GSH) was administered systemically by mouth. Five animals (Group 3) received vitamin E instead of glutathione. An additional 20 animals (Groups 4, 5, 6, and 7) were untreated, vehicle, glutathione, and vitamin E controls, respectively. Glutathione and vitamin E were given in doses of 10 mg/kg in 0.5 ml of mineral oil thrice weekly on days alternate to DMBA painting. Treatment by GSH and vitamin E reduced the number and size of tumors that were formed. Histopathologically, there were also fewer sites of dysplasia, carcinoma in situ, and early invasive epidermoid carcinoma than in the tumor control animals. The formalin-fixed and paraffin-embedded buccal pouch sections were stained immunohistochemically with use of monoclonal antibodies for cytokeratins. These included high-molecular-weight keratins (50,000-68,000 mol wt) 10, 13, and 8 (k10, k13, and k8, respectively). Oral carcinomas and dysplastic sites exhibited basal and suprabasal (spinous layer) high levels of k10, k13, and k8 staining. Treatment with GSH or vitamin E increased the suprabasal staining for high-molecular-weight keratins and reduced the protein expression for k10, k13, or k8. This pattern of staining was observed in dysplastic as well as in carcinoma sites. These results indicate that cytokeratin protein expression could contribute to a common biomarker analysis for chemoprevention.
使用7,12 - 二甲基苯并[a]蒽（DMBA）在仓鼠颊囊中诱发表皮样癌。在作为肿瘤对照的5只动物（第1组）中，右颊囊每周用DMBA（矿物油中的0.5%溶液）涂抹3次，持续14周。在5只动物（第2组）中，右颊囊用DMBA涂抹，并通过口服全身给予还原型谷胱甘肽（GSH）。5只动物（第3组）接受维生素E而非谷胱甘肽。另外20只动物（第4、5、6和7组）分别作为未处理、赋形剂、谷胱甘肽和维生素E对照。谷胱甘肽和维生素E以10 mg/kg的剂量溶于0.5 ml矿物油中，在与DMBA涂抹日交替的日子里每周给药3次。GSH和维生素E治疗减少了所形成肿瘤的数量和大小。组织病理学上，发育异常、原位癌和早期浸润性表皮样癌的部位也比肿瘤对照动物少。用细胞角蛋白单克隆抗体对福尔马林固定、石蜡包埋的颊囊切片进行免疫组织化学染色。这些抗体包括高分子量角蛋白（分子量50,000 - 68,000道尔顿）10、13和8（分别为k10、k13和k8）。口腔癌和发育异常部位在基底和基底上层（棘层）显示k10、k13和k8的高水平染色。用GSH或维生素E治疗增加了高分子量角蛋白的基底上层染色，并降低了k10、k13或k8的蛋白表达。这种染色模式在发育异常部位以及癌组织中均有观察到。这些结果表明细胞角蛋白蛋白表达可能有助于化学预防的共同生物标志物分析。
