IN VITRO GENOTOXICITY TESTING USING THE MICRONUCLEUS ASSAY IN CELL LINES, HUMAN LYMPHOCYTES AND 3D HUMAN SKIN MODELS.
The toxicological relevance of the micronucleus (MN) testis well defined: it is a multi-target genotoxic endpoint,assessing not only clastogenic and aneugenic events butalso some epigenetic effects, which is simple to score,accurate, applicable in different cell types. In addition, it ispredictive for cancer, amenable for automation and allowsgood extrapolation for potential limits of exposure orthresholds and it is easily measured in experimental bothin vitro and in vivo systems. Implementation of in vitromicronucleus (IVMN) assays in the battery of tests forhazard and risk assessment of potential mutagens/carcinogensis therefore fully justified. Moreover, the final draftof an OECD guideline became recently available for thistest. In this review, we discuss the prerequisites for anacceptable MN assay, including the cell as unit ofobservation, importance of cell membranes, the requirementof a mitotic or meiotic division and the assessment ofcell division in the presence of the test substance.Furthermore, the importance of adequate design ofprotocols is highlighted and new developments, in particularthe in vitro 3D human skin models, are discussed.Finally, we address future research perspectives includingthe possibility of a combined primary 3D human skin andprimary human whole blood culture system, and the needfor adaptation of the IVMN assays to assess the genotoxicpotential of new materials, in particular nanomaterials.
7th Amendment to the Cosmetics Directive, Aneugenic events, Clastogenic events, EpiDerm (EPI-200-MNA), Epigenetic effects, Genotoxicity testing, Interlaboratory reproducibility, Metabolic capability, Physiologically relevant assay, REACH, Reconstructed skin micronucleus (RSMN), Reproducibility, Validation, Xenobiotic metabolism
Cyclohexanone, Mitomycin C, N-ethyl-N-nitrosourea
Request a copy of this paper, click here.