Exposure to beef growth promoter in breast cancer

描述(由申请人提供)： 玉米赤霉醇(Z)是一种具有雌激素活性的非甾体类药物，被用作 美国牛肉和小牛肉行业的增长促进剂。因此，人们暴露在 通过饮食摄入来达到Z的直接和有意的结果 兽医专业人士将该化合物引入食用动物 代表肉牛业养殖户。我们的论点是， 从用Z处理过的食用动物中提取的食品，尤其是牛肉 对人类消费者的潜在健康影响，特别是在尊重 荷尔蒙敏感的器官。这一担忧源于我们自己的实验数据 使用从人类乳房细胞和组织中提取的体外模型 证明存在热稳定的生物学活性和雌激素活性 来自Z处理过的牛的肉的提取物。这些实验数据 在长期饮食暴露于低水平食物之间提供假定的联系 Z和乳腺癌的潜在风险。这项拟议的研究旨在 评估通过牛肉消费接触Z与乳房之间的关系 人类受试者的癌症。正常受试者和乳腺癌患者将 根据牛肉消费水平进行分类。乳房中的Z水平， 血、尿与相关机制分子标志物的表达水平 乳房组织中的含量将被确定为暴露和风险的指标 乳腺癌。从全国各地购买的牛肉产品中Z含量的测量 美国，生物活性的确认(有丝分裂活性；更改 基于机理的分子生物标记物在人和牛肉样品中的表达 旨在巩固牛肉消费、Z暴露和 乳腺癌风险。这项研究的具体目的是：(1)发展一种 用于商品肉类和人体中Z的常规检测的ELISA设计 组织和液体；(2)调查牛肉消费之间的关系， 乳腺癌患者乳房、血清和尿液中Z的水平 俄亥俄州立大学医院；(3)测量商业中的Z水平 从5个不同地区的超市购买到的牛肉产品 以及(4)利用已建立的体外模型系统 确认存在生物活性(有丝分裂活性；已更改 基于机制的分子生物标记物在人类标本中的表达 受试者和检测到Z水平的商品牛肉制品。这个 建议的研究利用我们不同的多学科专业知识在 生殖内分泌学、临床和外科肿瘤学、乳腺癌、 兽医学和药物化学来探讨我们的论点 食用牛肉可能会对人类健康构成风险。拟议的研究将把 牛肉生产实践、牛肉消费与人类乳腺癌 综合和全面的方法，将澄清 Z在乳腺癌中的暴露，确定潜在有价值的机制 分子生物标记物可能导致新的暴露评估工具 乳腺癌，为今后这方面的研究方向提供了肥沃的基础 重要领域，并提供可能对联邦政府有用的信息 监管机构在知情的情况下就 在牛肉中使用生长促进剂的现行法规和做法 注定要供人类食用。

DESCRIPTION (provided by applicant): Zeranol (Z) is a nonsteroidal agent with estrogenic activity that is used as a growth promoter in the U.S. beef and veal industries. Thus, people are exposed to Z via dietary intake as a consequence of the direct and intentional introduction of the compound into food animals by veterinary professionals on behalf of beef industry farmers. Our contention is that the consumption of food products, particularly beef, derived from food animals treated with Z has a potential health impact on human consumers, particularly with respect hormone-sensitive organs. This concern arises from our own experimental data using in vitro models derived from human breast cells and tissues which demonstrates the presence of heat-stable biological and estrogenic activity in extracts of meat derived from Z-treated cattle. These experimental data provide a putative link between the long-term dietary exposure to low-levels of Z and potential risk of breast cancer. The proposed study is designed to assess the relationship between exposure to Z via beef consumption and breast cancer in human subjects. Normal subjects and breast cancer patients will be categorized according to level of beef consumption. Levels of Z in breast, serum and urine and expression levels of mechanism-based molecular biomarkers in breast tissues will be determined as indicators of exposure and risk for breast cancer. Measurement of Z levels in purchased beef products from across the U.S., and confirmation of biological activity (mitogenic activity; altered expression of mechanism-based molecular biomarkers) in human and beef samples is aimed to solidify the association among beef consumption, Z exposure and breast cancer risk. The Specific Aims of the study are: (1) To develop an ELISA designed for the routine measurement of Z in commercial meats and human tissues and fluids; (2) To investigate relationships among beef consumption, levels of Z in breast, serum and urine, and breast cancer in patients of The Ohio State University Hospital; (3) To measure Z levels in commercially available beef products purchased in supermarkets from 5 different regions across the U.S.; and (4) To utilize established in vitro model systems to confirm the presence of biological activity (mitogenic activity; altered expression of mechanism-based molecular biomarkers) in specimens from human subjects and commercial beef products in which Z levels were detected. The proposed study utilizes our diverse multi disciplinary expertise in reproductive endocrinology, clinical and surgical oncology, breast cancer, veterinary medicine and medicinal chemistry to explore our contention that beef consumption may pose a human health risk. The proposed study will link beef production practices, beef consumption and human breast cancer in an integrated and comprehensive approach that will clarify the potential role of Z exposure in breast cancer, identify potentially valuable mechanism-based molecular biomarkers that could lead to new tools for exposure assessment in breast cancer, provide a fertile basis for future research directions in this important area, and provide information that may be useful to federal regulatory agencies in making informed decisions regarding the status of current regulations and practices in the use of growth promoters in beef destined for human consumption.