ASSESSMENT OF AIRWAY GENOTOXICITY POTENTIAL USING THE EPIAIRWAY IN VITRO HUMAN AIRWAY MODEL AND THE COMET ASSAY.

Determination of genotoxic potential is an important consideration for safety assessment of chemicals that may be inhaled following exposure to consumer products, occupational chemicals or environmental pollutants.   Commonly used in vitro genotoxicity assays produce a high rate of false positive results, limiting their practical utility for predicting human genotoxicity hazard.  For assessment  of organ-specific genotoxicity hazard, 3D in vitro human tissue models, which have in vivo-like barrier function and metabolic capability, and which allow for in vivo-like exposure, are expected to have improved biological relevance and predictive ability. Due to recently enacted legislative initiatives including REACH and the ban on animal testing of cosmetics by the 7th Amendment to the Cosmetics Directive, predictive organ-specific genotoxicity tests are urgently needed.  Previous work has focused on the development of skin specific genotoxicity tests including the micronucleus assay and the comet assay. In the current poster, we describe development of an airway specific genotoxicity assay using the EpiAirway in vitro human airway model and the comet assay.  The EpiAirway model is produced from normal human airway epithelial cells and reproduces the pseudo-stratified mucociliary phenotype of the in vivo proximal airways. The model has functional tight junctions and in vivo-like barrier properties as well as in vivo-like xenobiotic metabolizing capabilities.

Comet assay, EpiAirway-100, Genotoxicity, Genotoxicity assays

4-nitrophenol (4NP), 4-nitroquinoline 1 –oxide (4NQO), Acetone, Methylmethanesulfonate (MMS)