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， 北美最广泛使用的精神药物 甲基化 嘌呤最常在可乐、茶、巧克力和许多 处方药和非处方药。 尽管无处不在的 消费的药物，我们仍然不知道是否药物是一个 恶性肿瘤发生中的重要“生活方式”因素 疾病 在这项研究计划中，我们打算确定是否 实验室动物的慢性咖啡因消耗有助于 乳腺肿瘤的发生和/或进展。 在此提出的 研究中，我们选择了人类乳腺癌的动物模型， 在形态学和生理学上， 现有的啮齿动物模型。 这些人类疾病的模型是：1） 致癌物（DMBA）诱导的Sprague-Dawley大鼠乳腺癌， BD 2F 1小鼠; 2）激素（雌激素和孕激素）诱导的乳腺癌 GR小鼠中的癌和3）病毒诱导的（自发性）乳腺癌 在未经产和经产C3 H小鼠中。 此外，我们还打算审查 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，一个高 膳食脂肪水平是啮齿动物乳腺的有效刺激物 肿瘤发生 重要的是要确定是否慢性 咖啡因摄入可显著影响乳腺癌的发生 高脂肪饮食的活动。 我们将研究咖啡因与 和高脂饮食对DMBA诱导的大鼠乳腺癌模型的影响， 这种人类疾病有许多特征， 许多研究（例如，激素反应性，导管起源， 启动和升级阶段可以分开检查等）。 如果 长期摄入咖啡因可以持续增强 在人乳腺癌模型中的乳腺肿瘤发生是 在这些研究中进行了检查，然后有科学依据， 将被提供。 这项研究计划的主要推动力是 是由我们实验室最近的一份报告产生的， 一直观察到咖啡因的温和但显著的促进作用， 大鼠乳腺癌的发生。

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.