DNA DAMAGE IN MOUSE TUMORS EVAL BY IR SPECTROSCOPY

马林斯和其他人之前的工作，使用气相色谱-质谱仪 带有选择离子监测的光谱(GC-MS/SIM)等 近年来，傅里叶变换-红外光谱(FT-IR)联合应用 通过统计分析，证明了对 DNA碱基与磷酸脱氧核糖结构 致癌，甚至在有任何组织病理学证据之前 肿瘤。这些变化主要归因于自由基， 如羟基自由基(OH)。用这种方法获得的数据 有明显的区别，例如，肝脏和暴露于 被化学致癌物和鱼的肝脏污染的环境 从一个干净的参考区，在良性前列腺增生症(BPH) 和前列腺癌，以及乳房组织之间的 癌和乳房组织在缩小期间切除的大小 非癌性乳房。我们现在提议在两只不同的小鼠身上做实验 具有不同肿瘤病因的系统，化学诱导 横纹肌肉瘤与乳腺肿瘤病毒(MTV)相关性乳腺 癌症。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DNA细胞进行分析 人群从正常状态经历癌前阶段到原发阶段 肿瘤和转移。第二，我们将评估 自由基清除剂，以减少DNA碱基损伤，通过检测 傅立叶变换红外光谱，从而抑制/延缓致癌。第三, 我们将评估两种不同模式的化疗药物 使用FT-IR技术，影响可检测到的DNA损伤的作用，以及 试图将这与它们在肿瘤形成中的活性联系起来。

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.