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: 2723508
• 负责人: DONALD C MALINS
• 金额: $ 24.63万
• 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/2723508
• 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.

Malins 等人之前使用气相色谱-质谱进行的工作 具有选择离子监测功能的光谱测定 (GC-MS/SIM) 等 最近，傅里叶变换红外（FT-IR）光谱结合 通过统计分析，已经证明了深刻的改变 DNA 碱基和磷酸脱氧核糖结构 甚至在有任何组织病理学证据之前就已经发生癌变 肿瘤。 这些变化主要归因于自由基， 例如羟基自由基（OH）。 通过这种方法获得的数据 可以清楚地区分肝脏和暴露于环境的鱼的肝脏 受化学致癌物质和鱼肝污染的环境 来自良性前列腺增生 (BPH) 之间的干净参考区域 和前列腺癌，以及来自乳房的乳腺组织之间 缩小乳房大小期间切除的癌和乳腺组织 非癌性乳房。 We now propose experiments in two different mouse 化学诱导的具有不同肿瘤病因的系统 横纹肌肉瘤和乳腺肿瘤病毒 (MTV) 相关的乳腺 癌。 我们的首要目标是确认和扩展之前的工作 通过应用 FT-IR/统计技术来分析 DNA 作为细胞 人群从正常状态经过肿瘤前阶段转变为初级阶段 肿瘤和转移。 其次，我们要评估的能力 自由基清除剂，可减少 DNA 碱基损伤（经检测） FT-IR 光谱，从而抑制/延缓致癌作用。 第三， 我们将评估两种不同模式的化疗药物如何 使用 FT-IR 技术影响可检测的 DNA 损伤的作用，以及 试图将其与它们在肿瘤形成中的活性联系起来。