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Agonistic and Antagonistic effects of Zearalenone, an Etrogenic Mycotoxin, Human
Cancer Cell lines
Withanage GS, Murata H, Koyama T, Ishiwata I.
Zearalenone (ZEA) is a nonsteroidal estrogenic compound mainly produced by the
molds Fusarium graminearium and Fusarium culmorum found in a variety of host
plants and soil debris around the world. ZEA is usualy non-lethal to animals but
is important to livestock producers because its hyperestrogenic effects
adversely influence the reproductive performance of animals. There have been
suggestions of possible involvement of ZEA in the progression of breast
malignancies and tumors of the female reproductive tract in humans. The toxic or
stimulatory effects of ZEA and its metabolites alpha-zearalenol and
17-beta-estradiol on SKN, HHUAand HepG2 cells were studied using rapid
colorimetric MTT assay. In general, both concentrations of 17-beta-estradiol
(100M and 10 nM) were toxic to SKN and HHUA cell cultures. Both ZEA and alpha-zearalenol
stimulated the proliferation of SKN and HHUA cells. On HepG2 cells, lower
concentrations (10 nM) of 17-beta-estradiol and higher concentrations (100
microM) of ZEA exhibited toxic effects, whereas treatment with higher
concentrations of 17-beta-estradiol and lower concentration of ZEA did not show
toxic effects. A dose dependent antagonistic effect was observed when the cell
cultures were pre-incubated with ICI 182,780, a synthetic estrogen receptor
blocker, before estradiol or mycotoxin treatments.