HepaCometChip Enables SRP Research and Chemical Safety Testing

By Bevin P. Engelward

Director, MIT Superfund Research Program

A blind spot for high throughput genotoxicity assays is the inability to detect bulky lesions on DNA that have the potential to be carcinogenic. To overcome this limitation, Drs. Lizzie Ngo and Norah Owiti from the Engelward laboratory developed new methodologies for the CometChip, a high throughput comet assay developed at MIT. By incorporating hepatocytes, the platform can detect bulky lesions that are formed as a consequence of metabolic activation. Another challenge is that bulky lesions are not easily detected using the traditional comet assay, which reveals the presence of strand breaks but not bulky lesions. By incorporating inhibitors of DNA synthesis, the new assay traps repair intermediates, effectively enabling the cell to convert undetectable bulky lesions into detectable strand breaks. The assay is currently being used for a collaboration between an environmental science and engineering project and a biomedical project, where the goal is to identify novel PAH breakdown products and to test their biological impact. The new platform can also be used to screen for chemical safety and is described in a manuscript published in Nucleic Acids Research (DOI: 10.1093/nar/gkz1077). This work was featured in Technology NetworksScience Daily, the MIT News, and as an NIEHS Paper of the Month.