Time-dependent modulation of cyp1a gene transcription and EROD activity by musk xylene in PLHC-1 and RTG-2 fish cell lines

Musk xylene (MX) is a common synthetic nitromusk fragrance. Its high release in aquatic environments and evidence of bioaccumulation in biota suggest that it could have serious toxicological consequences for aquatic ecosystems. However, not much data is available on cellular pathways and mechanisms of toxicity in aquatic organisms. The aim of the present study was to investigate the interaction of MX with CYP1A by looking at gene transcription and EROD activity in two fish cell lines: PLHC-1 and RTG-2. Time-dependent (6 and 24 h) exposure experiments with three doses of MX (2, 4 and 20 μM) were performed also with co-exposure to B(a)P. Low cytotoxicity was observed in both cell lines. Reduction of cyp1a gene transcription was observed after 6 h with full dose-dependent recovery in 24 h in RTG-2 and partial recovery in PLHC-1. EROD activity was inhibited after 6 and 24 h of exposure except in PLHC-1 at 6 h at the two higher doses. MX did not alter CYP1A induction by B(a)P at gene transcription. A dose and time-dependent induction of GST activity was observed in PLHC-1 cells exposed to MX. These findings suggest that distinct signalling pathways not mediated by AhR and distinct regulatory mechanisms by CYP1A inducers are likely.