Regulatory Aspects and Guidelines for the use of Micronucleus Assays in Mammalian and Human Cells

Abstract

Micronucleus (MN) assays have become the most widely used and best validated biomarkers of DNA damage and chromosomal instability in human cells both in vitro and in vivo. To ensure consistent and reliable application of micronucleus assays within and across laboratories worldwide, it is essential to establish clear guidelines and detailed protocols and to test these in inter-laboratory validation exercises. This chapter focuses on (i) the process of the establishment of the approved OECD guideline 487 for using mammalian cell line and human lymphocyte micronucleus assays with or without cytokinesis-block using cytochalasin-B for the genotoxicity testing of chemicals; (ii) the guidelines approved by the International Atomic Energy Agency and World Health Organization, and the associated ISO Standard #17099 for the use of the lymphocyte cytokinesis-block micronucleus cytome (CBMN-cyt) assay for biodosimetry of occupational or accidental exposure to ionizing radiation and its validation in international inter-laboratory network studies; (iii) a road-map to achieve internationally accepted regulatory guidelines for the application of the lymphocyte CBMN-cyt assay to measure in vivo DNA damage induced by chemical genotoxin exposure and its justification based on recent reviews of all published studies and (iv) the current status of the use of exfoliated epithelial cell MN assays to measure DNA damage induced by exposure to chemical genotoxins in vivo and the knowledge gaps that need to be addressed before proceeding to a regulatory guideline.