We have previously shown that direct application of NAPQI to mouse Hepa-1c1c7 hepatoma cells triggers an Nrf2-driven stress response16, yet the relative inability of these and other immortalised liver cell lines to perform certain drug bioactivation reactions17 has rendered them unsuitable for investigating the role of reactive metabolite formation in the Nrf2 response to APAP in vitro. This evidence concerns the gene NFE2L2 and hepatocellular carcinoma.