Exposure to beef growth promoter in breast cancer

描述（由申请人提供）： Zeranol（Z）是一种具有雌激素活性的非甾体药物， 美国牛肉和小牛肉行业的增长促进剂。因此，人们暴露在 通过饮食摄入到Z，这是直接和故意的结果， 由兽医专业人员将该化合物引入食用动物， 牛肉产业的农民。我们的论点是， 食品，特别是牛肉，来源于用Z处理的食用动物， 对人类消费者的潜在健康影响，特别是 敏感器官。这种担忧来自我们自己的实验数据 使用来自人乳腺细胞和组织的体外模型， 证明了热稳定的生物活性和雌激素活性的存在， 来自Z处理的牛的肉提取物。这些实验数据 提供了一个假定的联系，长期饮食接触低水平的 和乳腺癌的潜在风险。拟议的研究旨在 评估通过食用牛肉和乳房接触Z之间的关系 癌症在人类受试者。正常受试者和乳腺癌患者将被 根据牛肉消费水平分类。乳房中的Z水平， 血清和尿液以及基于机制的分子生物标志物的表达水平 将确定乳腺组织中的放射性浓度，作为 乳腺癌测量从各地购买的牛肉产品中的Z水平 美国，和生物活性（促有丝分裂活性;改变的 表达的机制为基础的分子生物标志物）在人类和牛肉样品 旨在巩固牛肉消费、Z暴露和 乳腺癌风险。本研究的具体目的是：（1）建立一个 ELISA法测定市售肉类和人体中的Z 组织和液体;（2）调查牛肉消费之间的关系， 乳腺、血清和尿液中的Z水平与乳腺癌的关系 俄亥俄州州立大学医院;（3）测量商业上的Z水平 从5个不同地区的超市购买的牛肉产品 美国各地;和（4）利用已建立的体外模型系统， 确认存在生物活性（促有丝分裂活性;改变 基于机制的分子生物标志物的表达）在来自人的样本中 受试者和商业牛肉产品中检测到Z水平。的 拟议的研究利用我们多样化的多学科专业知识， 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， 食用牛肉可能对人体健康构成威胁。该研究将与 牛肉生产实践，牛肉消费和人类乳腺癌， 综合全面的办法，以澄清 乳腺癌中的Z暴露，确定潜在的有价值的机制 分子生物标志物，可能导致新的工具，暴露评估， 乳腺癌，为未来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 监管机构在作出知情决定的地位， 在牛肉中使用生长促进剂的现行法规和做法 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.