Assessing the effect of food mycotoxins on aromatase by using a cell-based system.

Zeranol, aflatoxin B1, zearalenone are mycotoxins that are commonly found as food contaminants. The chemical structures of zeranol and zearalenone resemble estrogen, and may disrupt hormone metabolism. The biosynthesis of estrogen is catalyzed by aromatase or CYP19. In the present study, effect of these mycotoxins on aromatase was evaluated by using 4 cell lines, i.e. the CYP19-overexpressing cells MCF-7aro, the placental cells JEG-3, the breast cells MCF-7, and the brain cells T98G. Our data indicated that zearalenone was a competitive inhibitor of aromatase with a K(i) value of 1 μM. As aromatase expression is promoter-specific and regulated by alternate splicing, we employed three cell lines for investigation. Our results showed that zearalenone and zeranol could suppress aromatase expression through promoters II and I.3. For aromatase transcription dictated by promoters I.f and I.1, the expression was not affected. Taken together, zearalenone was a potential aromatase inhibitor among the three mycotoxins tested. Furthermore, this 4-cell line approach could be employed in principle to screen for compounds inhibiting or inducing estrogen synthesis.