Waters M D, Stack H F, Jackson M A, Brockman H E
US Environmental protection Agency, Research Triangle Park, NC 27711, USA.
IARC Sci Publ. 1996(139):313-32.
The same short-term tests that have been used extensively to identify mutagens and potential carcinogens are increasingly being used to identify antimutagens and potential anticarcinogens. It is not yet known whether the inhibition of carcinogen-induced mutation is a good indicator of anticarcinogenicity, as the available data on the inhibition of both carcinogenicity and mutagenicity In vivo are still quite incomplete. Furthermore, in vitro tests will detect only those compounds that show an effect that is demonstrable in vitro, such as direct inhibition of the metabolism of the carcinogen or inactivation of the carcinogen by direct reaction. Thus it is essential to confirm putative antimutagenic activity observed in vitro through the use of animal models. Indeed, the interpretation of antimutagenicity data from short-term tests must be subjected to all of the considerations that apply in the interpretation of mutagenicity test results. Moreover, the experimental variable of the antimutagens used must be considered in addition to the variables of the mutagens and short-term tests used. To analyse published results on antimutagens in short-term tests, we have developed the concept of activity profile listings and plots for antimutagens - an approach already used successfully for mutagenicity data. The activity profiles permit rapid visualization of considerable data and experimental parameters, including the inhibition as well as enhancement of mutagenic activity. Here we focus on the use of this methodology to interpret antimutagenicity data for retinol and chlorophyllin against several classes of mutagens in short-term tests.
那些已被广泛用于识别诱变剂和潜在致癌物的短期测试，越来越多地被用于识别抗诱变剂和潜在抗癌剂。目前尚不清楚致癌物诱导的突变抑制是否是抗癌性的良好指标，因为关于体内致癌性和诱变性抑制的现有数据仍然相当不完整。此外，体外测试只能检测那些在体外显示出可证明效果的化合物，例如直接抑制致癌物的代谢或通过直接反应使致癌物失活。因此，通过使用动物模型来确认体外观察到的假定抗诱变活性至关重要。事实上，对短期测试中抗诱变数据的解释必须考虑到适用于诱变测试结果解释的所有因素。此外，除了所使用的诱变剂和短期测试的变量外，还必须考虑所使用的抗诱变剂的实验变量。为了分析短期测试中关于抗诱变剂的已发表结果，我们开发了抗诱变剂活性谱列表和绘图的概念——一种已成功用于诱变性数据的方法。活性谱允许快速直观地呈现大量数据和实验参数，包括诱变活性的抑制以及增强。在这里，我们重点介绍使用这种方法来解释视黄醇和叶绿酸在短期测试中对几类诱变剂的抗诱变数据。
