Mutagenicity test systems for the detection of chromosome aberrations in vivo.

In mutagenicity testing of pharmaceuticals it is advisable, whenever possible, to use in vivo mammalian systems where the pharmacokinetic properties of a drug would be more or less similar to those in man. However, although there are a number of different genetic endpoints which are important in mutagen testing, sufficiently validated, practical and well documented in vivo test systems exist only for structural chromosome aberrations. This paper provides an overview of existing in vivo test systems for the detection of chromosome aberrations. Emphasis has been laid on the functions, advantages and limitations of the three tests recommended in the guidelines of the European Community; first, the metaphase analysis assay, and, as alternatives, the micronucleus test and the dominant lethal test. These three tests are then also discussed from the viewpoint of our own practical experience.