The Snail Assay as an Alternative to the Rodent Hershberger Assay for Detecting Androgens and Anti-androgens

蜗牛测定作为啮齿动物赫什伯格测定的替代方法来检测雄激素和抗雄激素

• 批准号: G0900802/1
• 负责人: Susan Jobling
• 金额: $ 69.38万
• 依托单位: Brunel University London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0900802%2F1
• 关键词: Snail; Assay; Alternative; Rodent; Hershberger

Reproductive cancers and disorders and cancers are increasing in men and boys. Scientists suggest these problems may be caused by exposure to environmental pollutants found in residues on food, PVC plastics and in the linings of food cans. By fooling the body into thinking they are sex hormones, these chemical imposters break into the chemical hormone messenger system (endocrine system) and interfere with the signalling, causing reproduction and development to go awry. The government is developing policies towards endocrine disrupting chemicals using animal tests with rats and mice to test chemical safety. Medicines used to treat reproductive diseases and disorders are also put through the same tests in order to discover effective and safe new medicines with which to treat reproductive cancers and other diseases. Around 200,000 rodents and a smaller number of fish are used in chemical and drug testing of this kind annually. Although animal testing is essential for medical practice and the protection of consumers, it generates widespread public concern and reduction, refinement and replacement of vertebrate animals in chemical and drug testing is an acknowledged need. Replacement of rodents used in animal testing with less sentient invertebrate animals (like worms and flies) is one solution. Our common evolutionary heritage means that some of the mechanisms underlying medical conditions are the same in humans, flies and worms and that these animals could be used as alternatives to rats and mice to test chemicals. Currently, however, invertebrate models for reproduction are lacking. In order to fill this important gap, we will develop a model using the male snail reproductive organs. Snails share many structural and functional features with mammals, from the presence of similar reproductive genes to reproductive organs with similar functions such as the penis and the prostate. Preliminary studies have shown that human male hormones (androgens) stimulate the growth and development of these organs, and of undesireable tumour like growths on the reproductive organs just like in humans. We intend to expand on our existing knowledge of these phenomena and develop a properly validated system for testing pharmaceutical anti-androgens used to treat androgen-dependent cancers and for environmental safety testing of chemicals suspected of having harmful androgenic or anti-androgenic properties. We are hopeful that this assay will lead to a replacement of rodents in some animal tests.

男性和男孩的生殖系统癌症和疾病以及癌症正在增加。科学家们认为，这些问题可能是由于暴露于食品、PVC塑料和食品罐内衬中残留的环境污染物造成的。通过欺骗身体，使其认为它们是性激素，这些化学冒名顶替者闯入化学激素信使系统（内分泌系统）并干扰信号，导致生殖和发育出错。政府正在制定有关内分泌干扰化学品的政策，使用大鼠和小鼠进行动物试验，以测试化学品的安全性。用于治疗生殖系统疾病和失调的药物也要经过同样的测试，以便发现治疗生殖系统癌症和其他疾病的有效和安全的新药。每年约有20万只啮齿动物和少量鱼类被用于这类化学和药物测试。尽管动物试验对于医疗实践和保护消费者至关重要，但它引起了广泛的公众关注，并且在化学和药物试验中减少、改进和替代脊椎动物是公认的需要。用感觉较弱的无脊椎动物（如蠕虫和苍蝇）代替动物试验中使用的啮齿动物是一种解决方案。我们共同的进化遗产意味着，人类、苍蝇和蠕虫的一些潜在的医疗机制是相同的，这些动物可以作为大鼠和小鼠的替代品来测试化学品。然而，目前缺乏无脊椎动物的繁殖模型。为了填补这一重要空白，我们将开发一种使用雄性蜗牛生殖器官的模型。蜗牛与哺乳动物有许多共同的结构和功能特征，从存在相似的生殖基因到具有相似功能的生殖器官，如阴茎和前列腺。初步研究表明，人类雄性激素（雄激素）刺激这些器官的生长和发育，以及生殖器官上不期望的肿瘤样生长，就像人类一样。我们打算扩大我们现有的知识，这些现象，并开发一个适当的验证系统，用于测试药物抗雄激素用于治疗雄激素依赖性癌症和环境安全测试的化学品怀疑有有害的雄激素或抗雄激素特性。我们希望这种检测方法能够在某些动物试验中取代啮齿动物。