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

人类暴露于许多人造和自然发生的化学物质，其水平是我们从未遇到过的。其中相当一部分可能会导致癌症。因此，我们必须制订可靠的筛选程序，以确定哪些化学品可能致癌，并管制人类接触这些化学品的情况，这对人类健康至关重要。目前批准的系统集中在实验室动物癌症测试上，通常涉及活体大鼠和/或小鼠。然而，现在有大量的公众支持减少研究中使用的活动物数量，特别是在测试化学品的有害影响时。该项目旨在开发动物癌症测试的替代方案，使用培养的动物和人类细胞来测量致癌效应。最近，我们在布鲁内尔大学与制药公司AstaZeneca的同事合作，利用人类乳腺和仓鼠细胞培养物，开发了有前途的癌症细胞培养模型。早期的结果表明，这些新系统重现了一些已知在人类癌症发展中至关重要的重要步骤。在本项目中，将使用现代遗传技术进一步改进这些检测方法，并确定每种新的人类和仓鼠检测方法的相对优点和缺点。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。这反过来有望减少需要用于癌症测试的动物数量。研究结果将通过新闻发布会、大众媒体文章和适当网站向公众公布。

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.