DNA DAMAGE IN MOUSE TUMORS EVAL BY IR SPECTROSCOPY

通过红外光谱评估小鼠肿瘤中的 DNA 损伤

• 批准号: 6150347
• 负责人: DONALD C MALINS
• 金额: $ 28.63万
• 依托单位: PACIFIC NORTHWEST RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2003-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6150347
• 关键词: DNA damage; antioxidants; bioimaging /biomedical imaging; breast neoplasms; cellular oncology; chemical carcinogenesis; disease /disorder model; doxorubicin; free radical scavengers; histopathology; infrared spectrometry; laboratory mouse; metastasis; mouse mammary tumor virus; neoplasm /cancer chemotherapy; paclitaxel; preneoplastic state; rhabdomyosarcoma; statistics /biometry; viral carcinogenesis

Previous work by Malins and others, using gas chromatography-mass spectrometry with selected ion monitoring (GC-MS/SIM) and, more recently, Fourier transform-infrared (FT-IR) spectroscopy in combination with statistical analysis, has demonstrated profound modifications of DNA bases and phosphodrester-deoxyribose structures during carcinogenesis, even before there is any histopathological evidence of tumors. These changes have been attributed primary to free radicals, such as the hydroxyl radical (OH). Data obtained with this approach have sharply distinguished between, e.g., livers from fish exposed to an environment contaminated with chemical carcinogens and livers of fish from a clean reference area, between benign prostatic hyperplasia (BPH) and prostatic carcinoma, as well as between breast tissue from a mammary carcinoma and breast tissue removed during reduction of the size of noncancerous breast. We now propose experiments in two different mouse systems with different tumor etiologies, chemically induced rhabdomyosarcomas and mammary tumor virus (MTV)-assoicated breast carcinomas. Our first aim is to confirm and extend the previous work by applying the FT-IR/statistics technology to analyze DNA as cell populations change from normalcy via a preneoplastic stage to primary tumors and metastases. Second, we shall evaluate the ability of scavengers of free radicals to decrease DNA base damage, as detected by FT-IR spectroscopy, and thereby inhibit/delay carcinogenesis. Third, we shall evaluate how two chemotherapeutic drugs with different modes of action affect detectable DNA lesions, using the FT-IR technology, and attempt to correlate this with their activity in tumor formation.

马林斯和其他人以前的工作，使用气相色谱-质谱 选择离子监测（GC-MS/SIM）的光谱分析，以及更多 最近，傅里叶变换红外（FT-IR）光谱结合 通过统计分析，已经证明了对 DNA碱基和磷酸化脱氧核糖结构 甚至在有任何组织病理学证据表明 肿瘤的 这些变化主要归因于自由基， 例如羟基自由基（OH）。 用这种方法获得的数据 已经明确区分了，例如，鱼的肝脏暴露于 被化学致癌物和鱼肝污染的环境 从一个干净的参考区域，良性前列腺增生（BPH）之间 和前列腺癌，以及乳腺组织与乳腺癌之间的关系。 在缩小肿瘤大小的过程中切除的癌和乳腺组织 非癌性乳腺癌 我们现在建议在两种不同的小鼠中进行实验 具有不同肿瘤病因的系统，化学诱导 横纹肌肉瘤和乳腺肿瘤病毒（MTV）相关乳腺 癌 我们的第一个目标是确认和扩展以前的工作 应用FT-IR/统计技术对细胞DNA进行分析， 人群从正常经癌前阶段到原发性 肿瘤和转移。 第二，我们应该评估 清除自由基，以减少DNA碱基损伤，如检测到的 FT-IR光谱，从而抑制/延迟致癌作用。 第三、 我们将评估两种不同模式的化疗药物 作用影响可检测的DNA损伤，使用FT-IR技术， 试图将其与肿瘤形成中的活性联系起来。