TY - JOUR
T1 - Oestrogenic potencies of Zeranol, oestradiol, diethylstilboestrol, Bisphenol-A and genistein
T2 - implications for exposure assessment of potential endocrine disrupters
AU - Leffers, H
AU - Naesby, M
AU - Vendelbo, B
AU - Skakkebaek, N E
AU - Jørgensen, M
PY - 2001/5
Y1 - 2001/5
N2 - 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.
AB - 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.
KW - Amino Acid Transport Systems, Basic
KW - Animals
KW - Benzhydryl Compounds
KW - Breast Neoplasms/metabolism
KW - Carrier Proteins/genetics
KW - Cattle
KW - Diethylstilbestrol/pharmacology
KW - Estradiol/pharmacology
KW - Estrogens/pharmacology
KW - Food Contamination
KW - Gene Expression/drug effects
KW - Genistein/pharmacology
KW - Glutathione Transferase/genetics
KW - Growth Substances/pharmacology
KW - Humans
KW - Meat
KW - Membrane Proteins/genetics
KW - Monoamine Oxidase/genetics
KW - Phenols/pharmacology
KW - Polymerase Chain Reaction
KW - Proteins/genetics
KW - Transforming Growth Factor beta/genetics
KW - Trefoil Factor-1
KW - Tumor Cells, Cultured
KW - Tumor Suppressor Proteins
KW - Zeranol/blood
U2 - 10.1093/humrep/16.5.1037
DO - 10.1093/humrep/16.5.1037
M3 - Journal article
C2 - 11331657
SN - 0268-1161
VL - 16
SP - 1037
EP - 1045
JO - Human reproduction (Oxford, England)
JF - Human reproduction (Oxford, England)
IS - 5
ER -