CAFFEINE AND EXPERIMENTAL MAMMARY GLAND TUMORIGENESIS

咖啡因(1，3，7-三甲基黄嘌呤)具有可疑的区别 北美使用最广泛的精神药物。甲基化的 嘌呤最常用于可乐、茶、巧克力和许多 处方药和非处方药。尽管无处不在 服用该药物，我们仍不知道该药物是否是 “生活方式”因素在恶性肿瘤发生中的重要作用 疾病。在这项研究提案中，我们打算确定是否 实验动物长期摄入咖啡因导致 乳腺肿瘤的发生和/或发展。在本建议中 研究中，我们选择了人类乳腺癌的动物模型 在形态上和生理上是广谱的代表 现有的啮齿动物模型。这些人类疾病的模型是：1) 致癌物(DMBA)诱发SD大鼠乳腺癌和 BD2F1小鼠；2)激素(雌孕激素)诱导的乳腺 GR小鼠的癌和3)病毒诱导的(自发性)乳腺癌 在未分娩和经产的C3H小鼠中。此外，我们打算审查 另一种“生活方式”与咖啡因的潜在相互作用 因素，即高水平的膳食脂肪。很明显，一架高架 饮食脂肪水平是促进啮齿动物乳腺生长的有效因素 肿瘤发生学。重要的是要确定是否慢性 摄入咖啡因会显著影响乳腺肿瘤的发生 高脂饮食的活动。我们将研究咖啡因的相互作用 高脂饮食对DMBA诱发大鼠乳腺癌模型的影响 这种人类疾病具有许多吸引人的特征 大量研究(例如，激素反应性、导管起源、 可以分别检查启动和推广阶段，等等)。如果 长期摄入咖啡因可以持续地增强 人乳腺癌模型中乳腺肿瘤发生的研究进展 在这些研究中进行了审查，然后提出了值得关注的科学基础 将会被提供。这项研究提案的主要推动力 是由我们实验室最近的一份报告产生的，在报告中，我们 始终观察到咖啡因有轻微但显著的促进作用 体内大鼠乳腺癌变的研究。

Caffeine (1,3,7-trimethylxanthine) holds the dubious distinction of being the most widely used psychotropic drug in North America. The methylated purine is most often consumed in colas, teas, chocolates and numerous prescription and non-prescription drugs. Despite the ubiquitous consumption of the drug, we still do not know whether or not the drug is an important contributing "lifestyle" factor in the genesis of malignant disease. In this research proposal, we intend to determine whether or not chronic caffeine consumption by laboratory animals contributes to the genesis and/or progression of mammary gland neoplasias. In this proposed study, we have chosen animal models of human breast cancer which are morphologically and physiologically, representative of the broad spectrum of existing rodent models. These models of the human disease are: 1) carcinogen (DMBA) induced mammary carcinomas in Sprague-Dawley rats and BD2F1 mice; 2) hormone (estrogen and progesterone) induced mammary carcinomas in GR mice and 3) virus induced (spontaneous) mammary carcinomas in nulliparous and multiparous C3H mice. In addition, we intend to examine the potential interaction with caffeine of one more additional "lifestyle" factor, i.e., high levels of dietary fat. It is clear that an elevated level of dietary fat is a potent stimulant of rodent mammary gland tumorigenesis. It is important to determine whether or not chronic caffeine consumption can significantly influence the mammary tumorigenic activities of high fat diets. We will examine the interaction of caffeine and high fat diets on the DMBA induced rat mammary carcinoma model, a model of the human disease that has a number of features which have attracted much research (e.g., hormone responsiveness, ductal origin, ease in which initiation and promotion phases can be separately examined, etc.). If chronic caffeine consumption can be shown to consistently potentiate mammary gland tumorigenesis in the models of human breast cancer to be examined in these studies, then a scientific basis for significant concern will have been provided. The primary impetus for this research proposal was generated by a recent report from our laboratory in which we consistently observed a mild but significant promoting effect by caffeine of rat mammary gland carcinogenesis in vivo.