Interpretation of short-term test data: implications for assessment of chemopreventive activity

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.