VOLUNTARY EXERCISE AS MEANS OF MAMMARY CANCER PREVENTION

自愿锻炼作为预防乳腺癌的手段

• 批准号: 3192677
• 负责人: LEONARD A COHEN
• 金额: $ 10.88万
• 依托单位: INSTITUTE FOR CANCER PREVENTION
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-12-15 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3192677
• 关键词: benzanthracenes; bioassay; breast neoplasms; cancer prevention; carcinoma; chemical carcinogenesis; dietary carbohydrates; disease /disorder model; exercise; hormone related neoplasm /cancer; laboratory mouse; laboratory rat; metastasis; neoplasm /cancer transplantation; nutrition aspect of cancer; nutrition related tag; pituitary hormones; prolactin; radioimmunoassay; somatotropin; tumor promoters

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.

我们之前发现，自愿锻炼会产生一种 N-亚硝基甲基脲(NMU)对大鼠乳腺的抑制作用 肿瘤的发展。这项研究的目的是调查 自愿运动对儿童精神分裂症发生发展的抑制作用 (A)7，12-二甲基苯并(A)菲(DMBA)诱导的大鼠乳腺 癌症，(B)自发产生的小鼠乳腺癌，以及 (C)原代培养的大鼠乳腺肿瘤细胞的转移扩散 植入。对自愿锻炼的量化评估将由 特别设计的车轮保持架单元，配有活动装置 动物可以自由进出的轮子。这个 实验饮食被设计成模仿西方的高脂肪(HF) 饮食(40%的卡路里为脂肪)和低脂肪(LF)饮食(20%的 卡路里)，这是日本等低风险国家的典型特征。 实验方案的设计是为了测试 推广阶段的自愿练习(DMBA-使用NMU的模型 模型作为阳性对照)，总的肿瘤发生在病毒中- 诱导(C3H)小鼠模型及其进展(或转移)阶段 (R13762可移植乳腺肿瘤模型)。对于每种饮食 情况下，会有一个久坐不动的群体和一个活跃的群体。在… 终止、肿瘤潜伏期、频率、多重性和大小将 在DMBA和C3H模型中进行评估。肿瘤大小和总数 转移性肿瘤负担将在R13762模型中进行评估，并且 通过比较主动性判断运动的抑制效应 动物和它们久坐不动的同类。 作为探索终止时血清催乳素机制的一种手段 活动者和久坐者的催乳素和生长激素水平 将对这些组进行检测和比较。循环中的生长激素将 用标准的DIA程序进行测定。催乳素，一种已知的乳房 肿瘤促进剂，将通过两种不同的方法进行测量： 常规免疫测定法和NO2大鼠淋巴瘤生物测定法。这个 NO2法，检测有丝分裂原而不是免疫原性 催乳素的性质提供了一种确定是否新颖的手段 (不那么有丝分裂？)催乳素的分子形式在 中等强度到低强度运动的条件。 这项研究的总体目标是确定 自愿锻炼的保护作用仅限于一种特定的 致癌的种类、菌株、起始剂或阶段；或 它是否可以扩展到包括#年的乳腺癌发生 一般情况下，最终是人类乳腺癌。