Use of cultured human cells in short-term tests for chemical carcinogens.

Following the recent explosion in the number of designs for short-term assays for mutagens and carcinogens it appears worthwhile to take stock of the current situation and speculate about future developments. Over 400 strong, weak, and noncarcinogenic compounds have been examined by one or the other of the microbial tests, Drosophila assay, or the DNA fragmentation/DNA repair system of cultured mammalian cells. Between 80 and 90o of examined carcinogens give a positive response if checked with one test. If the results of several tests are pooled, only a very few carcinogens escape detection. In spite of these highly promising results, there is a reluctance on the part of regulatory agencies to accept wholeheartedly the rapid, inexpensive, and reproducible short-term bioassays. Why? The phylogenetic relationship between bacteria and man appears for some too remote to permit an extrapolation from microbial tests to human populations. Others doubt the validity of using point mutations as an endpoint, claiming that mutations may not play a role in neoplastic transformation and thus cannot be used as a relevant endpoint. One answer to these heretics could be to rank the various endpoints including, of course, carcinogenicity and to calculate a coefficient of rank correlation. Another answer would be to use several well chosen, short-term assays which complement each other. The Salmonella mutagenicity test in combination with activation systems (1) and the recombination assay of Kada (2) can be applied to mutagens/carcinogens found in the environment, in complex mixtures, or in body fluids of man. DNA fragmentation/DNA repair assays on cultured