Toxicological Sciences, Vol 52, 178-188, Copyright © 1999 by Society of Toxicology
JM Smeets, I van Holsteijn, JP Giesy and M van den Berg
Cultured hepatocytes of female carp (Cyprinus carpio) were coexposed for 4
days to 200 nM 17beta-estradiol (E2), and concentration ranges of nine
known Ah receptor (AhR) agonists: 2,3,7,8-tetrachlorodibenzo-p- dioxin
(TCDD), 3,3'4,4'5-pentachlorobiphenyl (PCB 126), 2,3'4,4'5-
pentachlorobiphenyl (PCB 118), beta-naphthoflavone (BNF), benzo(a)pyrene
(BaP), benzo(a)anthracene (BaA), diindolylmethane (DIM),
6-methyl-1,3,8-trichlorodibenzofuran (MCDF) and hexachlorobenzene (HCB).
TCDD caused a greater than 100-fold induction of cytochrome P4501A (CYP1A)
activity, measured as ethoxyresorufin O-deethylase (EROD), with an EC50 of
6 pM. Based on EC50 values, the order of potency as CYP1A inducers was TCDD
> PCB 126 > BNF > BaP > BaA > PCB 118. DIM and MCDF caused a
lower maximum CYP1A induction (< 9-fold), whereas HCB caused no EROD
induction at concentrations up to 6 microM. TCDD, PCB 126, BNF, BaP, and
DIM also caused a concentration-dependent suppression of the secretion of
the yolk protein vitellogenin (Vtg), relative to E2-treated hepatocytes.
Suppression of Vtg secretion was not directly correlated with EROD
activity, and the antiestrogenic effects occurred at higher concentrations
than the induction of CYP1A. This indicates that the anti-estrogenicity was
not caused by increased metabolism of E2 due to induction of CYP1A.
Nevertheless, the order of potency of the tested compounds for suppression
of Vtg secretion was comparable to the order of potency for CYP1A
induction. This concurrence suggests that the anti-estrogenicity of these
compounds is AhR-mediated, but does not involve CYP1A. This could be
relevant for feral fish populations, as they are frequently exposed to AhR
agonists, to an extent that AhR-mediated effects are observed.
ARTICLES
The anti-estrogenicity of Ah receptor agonists in carp (Cyprinus carpio) hepatocytes
Research Institute of Toxicology, Utrecht University, The Netherlands.
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