Toxicological Sciences, Vol 50, 206-213, Copyright © 1999 by Society of Toxicology
JM Smeets, I van Holsteijn, JP Giesy, W Seinen and M van den Berg
Estrogenic potencies of several xenoestrogens were determined in vitro,
using cultured hepatocytes from a genetically uniform male carp strain
(Cyprinus carpio). Estrogenicity was measured as induction of the yolk
protein precursor vitellogenin (Vtg), and compared to Vtg induction by
17beta-estradiol (E2). The order of estrogenic potency was: methoxychlor
(MXCL) > o,p-DDT > chlordecone approximately/= bisphenol-A
approximately/= 4-t-pentylphenol. Estrogenic potencies of these compounds
varied from 1 x 10(-3) to 1 x 10(-4) relative to E2. The synthetic estrogen
DES had a relative estrogenic potency of 0.5, whereas dieldrin,
beta-endosulfan, o,p-DDE, and toxaphene (technical mixture) did not induce
vitellogenesis at concentrations up to 100 microM. Experiments in which
cells were simultaneously exposed to E2 and these xenoestrogens showed that
the Vtg-inducing activities of E2 and 4-t-pentylphenol or bisphenol-A were
(partially) additive, whereas E2 antagonized the estrogenic effects of MXCL
and o,p-DDT. The effect of cytochrome P4501A (CYP1A)-induction on the
estrogenicity of MXCL was studied by co-exposing cells to
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD (10 pM) caused a greater
than 50-fold induction of CYP1A, measured as ethoxyresorufin O-deethylase
(EROD) activity, but Vtg induction by MXCL was not significantly affected.
This indicates that CYP1A is not involved in the bioactivation of MXCL to
more potent estrogenic metabolites in carp. The CARP-HEP (hepatocyte) assay
can detect xenoestrogens with a potency > or = 2 x 10(-5) relative to
E2. It allows simultaneous testing of more than 10 compounds for both
estrogenic and antiestrogenic effects, which makes it a promising tool for
the screening of suspected xenoestrogens.
ARTICLES
Estrogenic potencies of several environmental pollutants, as determined by vitellogenin induction in a carp hepatocyte assay
Research Institute for Toxicology, Utrecht University, The Netherlands.
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