Oestrogenic potencies of Zeranol, oestradiol, diethylstilboestrol, Bisphenol-A and genistein: implications for exposure assessment of potential endocrine disrupters.
We have compared the oestrogenic potency of the synthetic oestrogen Zeranol, used as a growth promoter in meat production, and five related compounds, with the potency of 17beta-oestradiol, diethylstilboestrol (DES), genistein, and Bisphenol-A. The potency was assayed by analysing differences in expression levels of endogenous oestrogen-regulated genes in human MCF7 cells, treated with different concentrations of the compounds. Zeranol, 17beta-oestradiol and DES were about equally potent, genistein was four to six orders of magnitude less potent than 17beta-oestradiol but an order of magnitude more potent than Bisphenol-A. There were gene specific differences, the PS2 and TGFbeta3 genes were about equally sensitive to Zeranol, 17beta-oestradiol and DES whereas a down-regulation of MRG1/p35srj could be detected at fmol/l concentrations of Zeranol whereas 17beta-oestradiol was several orders of magnitude less potent. GST mu3 was sensitive to fmol/l concentrations of 17beta-oestradiol but much less sensitive to Zeranol and DES. The very high potency of Zeranol compared with other potential endocrine disrupters suggests that Zeranol intake from beef products could have greater impact on consumers than the amounts of the known or suspected endocrine disrupters that have been found in food. Since little data is available in man, there is an urgent need for reliable measurements of the concentration of Zeranol in human serum after ingestion of meat products from treated animals.
Leffers
H
H
Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark. henrik.leffers@biobase.dk
Naesby
M
M
Vendelbo
B
B
Skakkebaek
N E
NE
Jørgensen
M
M
D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D001559:Benzhydryl Compounds; D001943:Breast Neoplasms / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002417:Cattle; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005506:Food Contamination; D015870:Gene Expression / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000235:genetics; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008460:Meat; D008565:Membrane Proteins / Q000235:genetics; D008995:Monoamine Oxidase / Q000235:genetics; D010636:Phenols / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D000071163:Trefoil Factor-1; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D015029:Zeranol / Q000097:blood / Q000494:pharmacology*; D000098826:Bisphenol A Compounds
D026923:Amino Acid Transport Systems, Basic; D001559:Benzhydryl Compounds; D002352:Carrier Proteins; D004054:Diethylstilbestrol; D004958:Estradiol; D004967:Estrogens; D019833:Genistein; D005982:Glutathione Transferase; D006133:Growth Substances; D008565:Membrane Proteins; D008995:Monoamine Oxidase; D010636:Phenols; D011506:Proteins; D016212:Transforming Growth Factor beta; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D015029:Zeranol; C051838:TFF1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds