Endocrine Abstracts

Fenhexamid is one of antifungal agents used in agricultural applications, which are present at measurable amounts in fruits and vegetables. Fenhexamid has been reported to act as an anti-androgen in an androgen receptor reporter assay in engineered human breast cancer cells. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which translocates into nucleus and dimerizes with aryl hydrocarbon receptor nuclear translocator (ARNT). Although function of ARNT is not clear, AhR–ARNT complex appears to be regulated by AHR response element (AHREs), dioxin-responsive element (DRE) or xenobiotic responsive element (XRE). In this study, we examined the effects of fenhexamid, a pesticide, on the expressions of AhR, CYP1A1, CYP1B1, ARNT, and p21 by RT-PCR analysis. In addition, the cell viability by fenhexamid was examined in BG-1 human ovarian cancer cells by MTT assay. To evaluate the ability of cell viability, BG-1 cells were cultured with a negative control (0.1% DMSO), 17β-estradiol (E₂; 1×10⁻⁹ M), 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD; 1×10⁻⁸ M), or fenhexamid (1×10⁻⁵ to 1×10⁻⁸ M). E₂ as a positive control markedly increased BG-1 cell proliferation compared to DMSO. In addition TCDD and fenhexamid increased BG-1 cell proliferation at the concentration of 1×10⁻8 and 1×10⁻⁵ M respectively. The transcriptional level of p21 was reduced at 6 h by E₂, TCDD, or fenhexamid, while its level was reversed at 24 h following their treatments. The mRNA expression of AhR was reduced by E₂, TCDD, or fenhexamid in a time-dependent manner, while its level was reversed in the presence of alpha-naphthoflavone, an AhR inhibitor. In contrast, the transcriptional level of ARNT appeared to be increased by E₂, TCDD, or fenhexamid. Taken together, these results indicate that fenhexamid may regulate AhR, ARNT and p21 to induce cell growth in BG-1 ovarian cancer cells expressing estrogen receptors. A further study will continue to examine disruptive effects of pesticides in estrogen receptor expressing cells or tissues.

Keywords: Pesticides, TCDD, fenhexamid, endocrine disrupting chemicals, ovarian cancer, aryl-hydrocarbon receptor