Author(s)

S. Focardi, C. Della Torre, M. Monti, T. Biagini & I. Corsi

Abstract

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 (cyp1a) 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 LC50 of 35.76μM for AHTN and LC50 123.6μM for MX. After 6h of exposure to MX, a dose-dependent reduction of cyp1a 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 cyp1a transcription levels compared to the inducer alone. After 6h AHTN determined a slight induction of cyp1a transcription reaching maximum induction of 2.3 folds respect to controls at 2μM. No modulation of cyp1a transcription was observed after 24h. Co-exposure to AHTN with B(a)P and PCB126 at 6h determined a 55% reduction of cyp1a 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 cyp1a basal transcription but did not alter cyp1a induction by B(a)P and PCB126. This suggests that MX cellular pathway is not mediated by AhR. On

Keywords

synthetic musks, PLHC-1, CYP1A