VOLUNTARY EXERCISE AS MEANS OF MAMMARY CANCER PREVENTION

我们以前已经发现，自愿行使行使 对N-亚硝基甲基脲（NMU）诱导大鼠乳腺癌抑制作用 肿瘤发展 本研究的目的是调查 自愿运动在发展中的抑制作用 (a)二甲基苯并蒽（DMBA）诱发大鼠乳腺癌 癌，（B）自发产生的小鼠乳腺癌，和 (c)大鼠乳腺癌细胞从原发灶转移扩散 植入 自愿运动的定量评估将通过 一个专门设计的轮笼单元， 动物可以自由进出的轮子。 的 实验饮食被设计成模仿高脂肪（HF）西方饮食， 饮食（40%的卡路里为脂肪）和低脂（LF）饮食（20%的卡路里为脂肪） 卡路里作为脂肪），典型的低风险国家，如日本。 实验方案的目的是测试的影响， 推广阶段的自愿练习（使用NMU的DMBA模式 模型作为阳性对照），在病毒- 诱导（C3 H）小鼠模型和进展（或转移）期 （R13762可移植乳腺肿瘤模型）。 对于每种饮食 在这种情况下，会有一个久坐的群体和一个活跃的群体。 在 终止、肿瘤潜伏期、频率、多样性和大小将 在DMBA和C3 H模型中进行评估。 肿瘤大小和总数 将在R13762模型中评估转移性肿瘤负荷， 运动的抑制作用是通过比较活动的 动物与它们久坐不动的同类。 作为探索机制的一种手段，在终止时，血清催乳素 (PRL)和生长激素（GH）水平在活动和久坐 将对各组进行测定和比较。 循环GH将是 通过标准DIA程序测定。 催乳素，一种已知的乳腺激素 将通过两种不同的方法测量肿瘤促进剂： 常规免疫测定和No2大鼠淋巴瘤生物测定。 的 No2检测，检测促有丝分裂而非免疫原性 催乳素的性质提供了一种手段，以确定是否新的 (less促有丝分裂的？）PRL的分子形式在 中等至低强度运动的条件。 本研究的总体目标是确定 自愿锻炼的保护作用仅限于特定的 种属、菌株、引发剂或致癌阶段，或 它是否可以扩展到包括乳腺癌的发生， 最终导致人类乳腺癌。

We have previously found that voluntary exercise exerts a suppressive effect on N-nitrosomethylurea (NMU)-induced rat mammary tumor development. The purpose of this study is to investigate the inhibitory role played by voluntary exercise in the development of (a) the 7,12-dimethylbenz(a)anthracene (DMBA) induced rat mammary carcinoma, (b) spontaneously generated mouse mammary carcinoma, and (c) the metastatic spread of rat mammary tumor cells from a primary implant. Quantitative assessment of voluntary exercise will be by a specially designed wheel cage unit equipped with an activity wheel to which animals have free access to and egress from. The experimental diets are designed to mimic the high-fat (HF) western diet (40% of calories as fat) and a low-fat (LF) diet (20% of calories as fat), typical of low risk countries such as Japan. The experimental protocols are designed to test the effects of voluntary exercise on the promotion phase (DMBA-model using the NMU model as a positive control), overall tumorigenesis in a virally- induced (C3H) mouse model and the progression (or metastatic) phase (R13762 transplantable mammary tumor model). For each dietary condition, there will be a sedentary and an active group. At termination, tumor latency, frequency, multiplicity and size will be assessed in the DMBA and C3H models. Tumor size and total metastatic tumor burden will be assessed in the R13762 model, and the inhibitory effects of exercise determined by comparing active animals with their sedentary counterparts. As a means to explore mechanisms, at termination, serum prolactin (PRL) and growth hormone (GH) levels in the active and sedentary groups will be assayed and compared. Circulating GH will be assayed by standard DIA procedures. Prolactin, a known mammary tumor promoter, will be measured by two different methods: the conventional immunoassay and the No2 rat lymphoma bioassay. The No2 assay, which tests the mitogenic rather than the immunogenic properties of prolactin provides a means to determine whether novel (less mitogenic?) molecular forms of PRL are released under conditions of moderate to low-intensity exercise. The overall goal of this study is to determine whether the protective effect of voluntary exercise is limited to a particular species, strain, initiating agent or stage of carcinogenesis, or whether it can be extended to encompass mammary carcinogenesis in general and ultimately human breast cancer.