Development and validation of mechanisms-based in vitro transformation assays for carcinogen screening

用于致癌物筛查的基于机制的体外转化测定的开发和验证

• 批准号: G0800697/1
• 负责人: Robert Newbold
• 金额: $ 38.1万
• 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=G0800697%2F1
• 关键词: Development; validation; mechanisms; based; vitro

Humans are exposed to many man-made and naturally occurring chemicals at levels we have never before encountered. A significant number of these can be expected to cause cancer. It is therefore of vital importance for human health that we have in place reliable screening procedures to establish which chemicals have cancer-causing potential, and to regulate human exposure to them. Currently approved systems are centred on laboratory animal cancer tests, usually involving live rats &/or mice. However, there is now enormous public support for reducing the numbers of live animals used in research, particularly in the testing of chemicals for harmful effects. This project has been designed to develop alternatives to animal cancer testing, using instead animal and human cells grown in culture to measure cancer-causing effects. Recent work by us at Brunel University, working with colleagues in the drug company AstaZeneca, has resulted in the development of promising cell culture models for cancer, using human breast and hamster cell cultures. Early results indicate that these new systems reproduce some of the important steps known to be critical in human cancer development. In this project, these assays will be improved further using modern genetic techniques, and the relative advantages and disadvantages of each of the new human and hamster assays determined. By this means, a new generation of cell culture-based tests will be produced that can be incorporated into existing screening programmes. This in turn is expected to lead to a reduction in the numbers of animals that need to be used in cancer testing. The results of the study will be communicated to the general public through press conferences, articles in the popular media, and via appropriate websites.

人类暴露在许多人造和自然产生的化学物质中的水平是我们以前从未遇到过的。其中很大一部分可以预期会致癌。因此，对人类健康至关重要的是，我们必须制定可靠的筛查程序，以确定哪些化学品具有致癌潜力，并对人类接触这些化学品进行监管。目前批准的系统集中在实验室动物癌症测试上，通常涉及活鼠和/或小鼠。然而，现在有巨大的公众支持减少用于研究的活动物的数量，特别是在测试化学品的有害影响方面。该项目旨在开发动物癌症测试的替代方法，使用在培养中生长的动物和人类细胞来衡量致癌效应。最近，我们在布鲁内尔大学与阿斯利康制药公司的同事合作，利用人类乳房和仓鼠细胞培养，开发出了有前景的癌症细胞培养模型。早期结果表明，这些新系统复制了一些已知在人类癌症发展中至关重要的重要步骤。在这个项目中，这些测试将使用现代基因技术进一步改进，并确定每一种新的人类和仓鼠测试的相对优势和劣势。通过这种方式，将产生新一代基于细胞培养的测试，可以纳入现有的筛查计划。这反过来预计将导致癌症测试所需动物数量的减少。研究结果将透过记者招待会、大众传媒的文章和适当的网站向公众公布。