, 1997a and Mace TSA HDAC research buy et al., 1997b). These cell lines have been mainly used for the toxicological assessment of single compounds ( Mace et al., 1994, Van Vleet et al., 2002 and Nichols et al., 2003). Although useful for the toxicity evaluation of single compounds, genetically engineered cell lines have toxicity testing limitations with complex mixtures and compounds with unknown metabolic pathway. The complex mixture could contain various pro-toxicants bioactivated by multiple CYPs. Nevertheless, pro-toxicants which are metabolised

by CYP1A1/1B1 enzymes such as PAHs could be bioactivated in pre-induced BEAS-2B cultures. In this study CYP1A1/1B1 gene expression and enzyme activity were induced using TCDD, however, other xenobiotics such as B[a]P have been used previously BTK signaling pathway inhibitor to induce these isoforms ( Nebert et al., 1993 and Tsuji and Walle, 2006). It is important to consider that the BEAS-2B cell line has a wider application for biological endpoint

assessment such as DNA damage and repair mechanisms in vitro. The non-cancerous phenotype and wild-type p53 status of the BEAS-2B cell line makes them an ideal cell system in cell transformation research ( Reddel et al., 1988, Petitjean et al., 2007 and IARC TP53, 2013). Moreover, the “oncogenic stress” exhibited by pre-malignant and cancer tissues could affect the measure of certain biomarkers of DNA damage such as the γH2AX ( Svetlova et al., 2010). The BEAS-2B cell line has also been selected as a cell system in the study of nanomaterials cellular transport and intracellular response ( Gilbert et al., 2012 and Ekstrand-Hammarstroem et al., 2012). During this study a number of well-characterized cell lines were used in parallel with the same treatment conditions. The A549 cell line was Methane monooxygenase selected

as a lung carcinoma-derived cell system for comparison purpose while the HepG2 and HepaRG cell lines were used as ‘positive control’ with a more extensive cytochrome P450 enzyme activity. A549 cells showed a small number of up-regulated genes in basal cultures such as AKR1B10 and AKR1C2 known to be associated with the cell line’s tumorigenic origin ( Quinn et al., 2008). As expected, in pre-induced cultures CYP1A1 and CYP1B1 genes were up-regulated (260-fold and 14-fold increase respectively). Interestingly, in our study the up-regulation of these genes was not translated into enzyme activity. The lack of CYP1A1/1B1 enzyme activity has been observed previously ( Newland et al., 2011). With respect to the results obtained for HepG2 and HepaRG cells, we observed that HepaRG express more genes involved in phase I and phase II metabolism than HepG2. Our results concur with data published previously ( Gerets et al., 2012 and Jennen et al., 2010). Our data on BEAS-2B have shown a different profile to the data published recently by Courcot et al.