ROLE OF ANTIOXIDANT ENZYMES IN ORAL CANCER

抗氧化酶在口腔癌中的作用

• 批准号: 6104875
• 负责人: LARRY OBERLEY
• 金额: $ 11.78万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104875
• 关键词: aging; antineoplastics; antioxidants; athymic mouse; catalase; chemical carcinogen; chemical carcinogenesis; cytotoxicity; enzyme activity; enzyme induction /repression; free radical scavengers; genetic translation; glutathione peroxidase; hamsters; immunocytochemistry; neoplastic process; northern blottings; oral pharyngeal neoplasm; oxidative stress; phenotype; southern blotting; superoxide dismutase; tissue /cell culture; transfection; western blottings

A high incidence of oral cancer is associated with aging. This project's long-term objectives are to develop better prevention and treatment strategies for oral cancer. We hope to accomplish this objective by modulating antioxidant enzymes (copper and zinc-containing superoxide dismutase [Cu-ZnSOD], manganese-containing superoxide dismutase [MnSOD], catalase [CAT], and glutathione peroxidase [GPX]) in cells. This proposal is intended to examine the role of the antioxidant enzymes and, in particular, MnSOD, in oral cancer. To our knowledge, there has been no work performed to date on these enzymes in oral tissues. Thus, we first propose to determine using the techniques of immunohistochemistry if the levels of any of the antioxidant enzymes change during chemical carcinogenesis in the hamster cheek pouch model. The reason(s) for any changes in these enzymes in both hamster and human oral tumors will then be determined at the molecular level; this will be accomplished using enzyme activity assays, Western, Northern, and Southern blotting. Last, the effects of transfecting sense and antisense MnSOD cDNA into cultured oral tumor cell lines on sensitivity to oxidative stress and on the malignant phenotype will be studied. Oxidative stress sensitivity will be determined by measuring survival after exposure to four antitumor agents (adriamycin, bleomycin, tumor necrosis factor and ionizing radiation). The malignant phenotype will be measured both in vitro (by tests such as growth in soft agar) and in vivo (by injecting cells into nude mice or syngeneic animals). Our studies will help to determine the mechanism of oral carcinogenesis and thus may suggest which antioxidants may be of particular value in preventing this cancer. Oral cancer remains a treatment problem. Information on modulation of MnSOD activity will tell us whether such manipulation could be of use in cancer therapy to eliminate tumor drug resistance or to protect normal tissue. Moreover, increasing MnSOD might be used for differentiation therapy of oral tumors, since our recent work suggests that such an approach could be useful in treating human melanoma. Thus, this proposal has relevance to both cytotoxic and differentiation therapy of cancer.

口腔癌的高发病率与衰老有关。 这个项目是 长期目标是发展更好的预防和治疗 口腔癌的策略。 我们希望通过 调节抗氧化剂酶（含铜和锌的超氧化物 歧化酶[Cu-Znsod]，含锰的超氧化物歧化酶[MNSOD]， 细胞中的过氧化氢酶[CAT]和谷胱甘肽过氧化物酶[GPX]）。 这 建议旨在检查抗氧化剂酶的作用，并检查 特别是在口腔癌中的MNSOD。 据我们所知，已经存在 至今未在口腔组织中的这些酶进行的工作。 因此，我们 首先建议使用免疫组织化学技术 如果任何抗氧化剂的水平在化学期间变化 仓鼠脸颊袋模型中的致癌作用。 任何原因的原因 然后，仓鼠和人口腔肿瘤中这些酶的变化将 在分子水平上确定；这将使用 酶活性测定，西部，北部和南部印迹。 最后的， 转染意义和反义MNSOD cDNA的影响 口服肿瘤细胞系对氧化应激的敏感性以及在 将研究恶性表型。 氧化应激灵敏度将 通过测量暴露于四个抗肿瘤后的存活来确定 药物（Adrimycin，博来霉素，肿瘤坏死因子和电离因子 辐射）。 恶性表型将在体外测量（通过 诸如软琼脂中生长的测试）和体内（通过将细胞注入到 裸小鼠或同性动物）。 我们的研究将有助于确定口服癌变的机制 因此可能建议哪种抗氧化剂在 防止这种癌症。 口腔癌仍然是一个治疗问题。 有关MNSOD活动调制的信息将告诉我们是否这样 操纵可能用于癌症治疗以消除肿瘤药物 阻力或保护正常组织。 而且，增加的mnsod可能 自我们最近的工作以来，可用于口腔肿瘤的分化治疗 表明这种方法对于治疗人可能很有用 黑色素瘤。 因此，该提案与细胞毒性和 癌症的分化治疗。