Figure 8
B[a]P metabolism by phase I and II XMEs is disturbed in HepaRG cells by steatosis and ethanol co-exposure. Non-steatotic (−FA) and steatotic (+FA) HepaRG cells were untreated (C) or treated with 2.5 µM B[a]P (B), 25 mM ethanol (E) or a combination of both toxicants (BE). At the end of the 14-day toxicant exposure and after a 15-minute washout, B[a]P metabolites were analyzed in the culture media after an acute incubation of 25 µM B[a]P with or without 5 mM salicylamide, a strong inhibitor of phase II XMEs. (a) Examples of two representative HPLC chromatograms corresponding to non-steatotic cells treated for 14 days with B[a]P, and then acutely exposed to B[a]P (B) or B[a]P with salicylamide (B + Sali). (b) Amount of B[a]P trans-7,8-dihydrodiol (peak 1 on panel a) assessed by its AUC and normalized to the total cellular protein content. (c) Amount of 3-OH-B[a]P-glucuronide (peak 2 on panel a) assessed by its AUC and normalized to the total cellular protein content. (d) Ratio of the amount of B[a]P trans-7,8-dihydrodiol to the amount of all detected metabolites. Results are means ± SEM for at least three independent cultures. #Significantly different from non-steatotic cells; *Significantly different from untreated non-steatotic or steatotic cells; aSignificantly different from non-steatotic or steatotic cells treated by ethanol only; bSignificantly different from non-steatotic or steatotic cells treated by B[a]P only.
