Synthetic musks fragrances in the aquatic environment: in vitro toxicological studies of their biotransformation and potential negative effects

摘要

The aim of the present study was to investigate the interaction of musk xylene (MX) and Tonalide (AHTN) with CYP1A by looking at gene transcription (cypla) and EROD activity in Poeciliopsis lucida hepatoma cell line (PLHC-1). MX and AHTN were studied individually and combined with classical inducer of CYP1A as B(a)P and PCB126. After 24h of exposure a different cytotoxicity has been observed with an LC_(50) of 35.76μM for AHTN and LC_(50) 123.6μM for MX. After 6h of exposure to MX, a dose-dependent reduction of cypla was observed respect to controls. At 24h, the same pattern was observed but with slight induction at the lowest concentration (2μM) and a dose-dependent reduction at the higher concentrations. Co-exposure to MX with B(a)P did not alter cypla transcription levels compared to the inducer alone. After 6h AHTN determined a slight induction of cypla transcription reaching maximum induction of 2.3 folds respect to controls at 2μM. No modulation of cypla transcription was observed after 24h. Co-exposure to AHTN with B(a)P and PCB126 at 6h determined a 55% reduction of cypla transcription respect to inducers alone which recovered at 24h. At 24h, MX caused a dose-dependent decrease of EROD activity. No modulation of EROD activity was detectable at 6h and 24h of exposure to AHTN. Co-exposure with both MX and AHTN did not alter EROD activity induced by B(a)P and PCB126. Results suggest different toxicological properties of MX and AHTN toward CYP1A in PLHC-1. MX reduced cypla basal transcription but did not alter cypla induction by B(a)P and PCB126. This suggests that MX cellular pathway is not mediated by AhR. Onthe contrary AHTN did not alter significantly cypla basal levels but decreased cypla induction by B(a)P and PCB126. A potential role of AHTN as competitive antagonist of AhR could thus be hypothesized.