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J.Health Sci., 50(6), 581-587, 2004
1-Chloro-2,4-Dinitrobenzene Stimulates the Estrogenic Activity in MCF-7 Cells
Joohee Jung, Kunie Ishida, Shigehiro Osada, Jun-ichi Nishikawa, and Tsutomu
Nishihara*
Laboratory of Environmental Biochemistry, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita,
Osaka 565-0871, Japan
The estrogenic effect of chemicals, including 1-chloro-2,4-dinitrobenzene (CDNB), in the combination with
17beta-estradiol (E2) was screened by a reporter gene assay using breast cancer cells (MCF-7). It was found that CDNB
stimulated E2-induced transcriptional activity of estrogen receptor (ER) and down-regulated both ER protein and
mRNA. However, CDNB alone and CDNB metabolite(s) showed no estrogenic activity and no binding activity to
ER, suggesting an indirect pathway other than ER. CDNB gave no transcriptional activity for an aryl hydrocarbon
receptor (AhR), suggesting no possibility of a pathway through cross-talk between AhR and ER. On the other hand,
CDNB enhanced the mitogen activated protein kinase (MAPK) pathway, suggesting estrogenic action
via MAPK. These results indicated that CDNB possessed estrogen-like activity in the transcription and regulation of ER though
a different pathway from E2.
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