In Vivo Rodent Micronucleus Assay

Abstract

Genotoxicity plays an important role for the safety evaluation of chemicals. Chromosomal aberration is one of two major end points of genotoxicity. The rodent haematopoietic cell micronucleus assay is most widely used as an in vivo test to evaluate structural and numerical chromosomal aberrations. The historical aspects of the development of the in vivo micronucleus test, the mechanism of micronucleus formation, and the characteristics of the test are reviewed. One of the limitations of the micronucleus assay is the use haematopoietic cells and it is desired to develop the genotoxic method targeted at cells other than haematopoietic cells. The micronucleus assay using cells other than bone marrow cells, for example using liver, skin, testis, and colon cells, has been developed and validated successfully. The validation studies have been organized as collaborative studies of the Mammalian Mutagenicity Study Group belonging to the Japanese Environmental Mutagen Society and have been published. The other recent development of the micronucleus test is automated evaluation systems. Image analysis and flow cytometry were introduced to the test system with great success. These automated methods are being validated for regulatory purposes. The in vivo multiple end point assay system, which is more efficient, is also discussed here. When we use transgenic mutagenicity model animals in the micronucleus assay, we can obtain information on both gene mutation and chromosomal aberrations concomitantly, and possibly on DNA damage when the micronucleus assay is combined with the comet assay. Such a multiple end point genotoxicity assay system should be highly appreciated from the viewpoint of animal welfare.