Selective estrogenicity in orally exposed transgenic male mice of compounds known to be estrogenic in vitro

M.G.R. ter Veld, P.T. van der Saag, I.M.C.M. Rietjens, A.J. Murk

Research output: Chapter in Book/Report/Conference proceedingAbstractAcademic

Abstract

Transgenic reporter gene mice carrying a 3xERE-tataluc- insulated construct were exposed to compounds found to be estrogenic in vitro. Transgenic male mice, chosen for their relative low background levels of circulating estrogens, were fed a phyto-estrogen free diet. They were housed individually and exposed orally via custard (0.5 ml/day) to either 0.3 and 1 mg/kg 17- estradiol dipropionate (EP), 10 and 50 mg/kg bisphenol A (BPA), 10 and 50 mg/kg nonylphenol (NP), 30 and 100 mg/kg di-isoheptyl phthalate (DIHP), 30 and 100 mg/kg di (2-ethylhexyl) phthalate (DEHP), 30 and 100 mg/kg di (2-ethylhexyl) adipate (DEHA), 5 and 50 mg/kg p,p -dichlorodiphenyl-dichloroethylene (DDE) and 1.6 and 16.6 mg/kg quercetin or solvent control. Fourteen hours later the mice were sacrificed and tissues including liver, pituitary, brain, testes and bone were isolated and frozen immediately at -80 ¿C. Maximal luciferase activity, normalized for protein, was induced by 1 mg/kg EP in the liver (5400-fold), while this was 2-times lower at 0.3 mg EP/kg. Several compounds that were estrogenic in vitro were not estrogenic in vivo. However, tissue specific modulation of luciferase expression was found for some compounds, especially BPA induced luciferase in the liver and kidneys. Nonylphenol slightly induced luciferase in the liver and kidneys. Relative few compounds were estrogenic in vivo. In vitro the studied compounds are at least 104 less estrogenic than E2, this might explain the relative small amount of estrogenic compounds in vivo, as relative low concentrations were tested compared to our in vitro study
LanguageEnglish
Title of host publicationAbstracts of the Dutch toxicology days, 13th-14th June 2006
Pages174 (1)
Volume161
Publication statusPublished - 2006

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Luciferases
Transgenic Mice
Liver
Dichlorodiphenyl Dichloroethylene
Kidney
Phytoestrogens
Quercetin
Reporter Genes
Testis
Estrogens
Diet
In Vitro Techniques
Brain
Proteins
phthalic acid

Cite this

ter Veld, M. G. R., van der Saag, P. T., Rietjens, I. M. C. M., & Murk, A. J. (2006). Selective estrogenicity in orally exposed transgenic male mice of compounds known to be estrogenic in vitro. In Abstracts of the Dutch toxicology days, 13th-14th June 2006 (Vol. 161, pp. 174 (1))
ter Veld, M.G.R. ; van der Saag, P.T. ; Rietjens, I.M.C.M. ; Murk, A.J. / Selective estrogenicity in orally exposed transgenic male mice of compounds known to be estrogenic in vitro. Abstracts of the Dutch toxicology days, 13th-14th June 2006. Vol. 161 2006. pp. 174 (1)
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abstract = "Transgenic reporter gene mice carrying a 3xERE-tataluc- insulated construct were exposed to compounds found to be estrogenic in vitro. Transgenic male mice, chosen for their relative low background levels of circulating estrogens, were fed a phyto-estrogen free diet. They were housed individually and exposed orally via custard (0.5 ml/day) to either 0.3 and 1 mg/kg 17- estradiol dipropionate (EP), 10 and 50 mg/kg bisphenol A (BPA), 10 and 50 mg/kg nonylphenol (NP), 30 and 100 mg/kg di-isoheptyl phthalate (DIHP), 30 and 100 mg/kg di (2-ethylhexyl) phthalate (DEHP), 30 and 100 mg/kg di (2-ethylhexyl) adipate (DEHA), 5 and 50 mg/kg p,p -dichlorodiphenyl-dichloroethylene (DDE) and 1.6 and 16.6 mg/kg quercetin or solvent control. Fourteen hours later the mice were sacrificed and tissues including liver, pituitary, brain, testes and bone were isolated and frozen immediately at -80 ¿C. Maximal luciferase activity, normalized for protein, was induced by 1 mg/kg EP in the liver (5400-fold), while this was 2-times lower at 0.3 mg EP/kg. Several compounds that were estrogenic in vitro were not estrogenic in vivo. However, tissue specific modulation of luciferase expression was found for some compounds, especially BPA induced luciferase in the liver and kidneys. Nonylphenol slightly induced luciferase in the liver and kidneys. Relative few compounds were estrogenic in vivo. In vitro the studied compounds are at least 104 less estrogenic than E2, this might explain the relative small amount of estrogenic compounds in vivo, as relative low concentrations were tested compared to our in vitro study",
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ter Veld, MGR, van der Saag, PT, Rietjens, IMCM & Murk, AJ 2006, Selective estrogenicity in orally exposed transgenic male mice of compounds known to be estrogenic in vitro. in Abstracts of the Dutch toxicology days, 13th-14th June 2006. vol. 161, pp. 174 (1).

Selective estrogenicity in orally exposed transgenic male mice of compounds known to be estrogenic in vitro. / ter Veld, M.G.R.; van der Saag, P.T.; Rietjens, I.M.C.M.; Murk, A.J.

Abstracts of the Dutch toxicology days, 13th-14th June 2006. Vol. 161 2006. p. 174 (1).

Research output: Chapter in Book/Report/Conference proceedingAbstractAcademic

TY - CHAP

T1 - Selective estrogenicity in orally exposed transgenic male mice of compounds known to be estrogenic in vitro

AU - ter Veld, M.G.R.

AU - van der Saag, P.T.

AU - Rietjens, I.M.C.M.

AU - Murk, A.J.

PY - 2006

Y1 - 2006

N2 - Transgenic reporter gene mice carrying a 3xERE-tataluc- insulated construct were exposed to compounds found to be estrogenic in vitro. Transgenic male mice, chosen for their relative low background levels of circulating estrogens, were fed a phyto-estrogen free diet. They were housed individually and exposed orally via custard (0.5 ml/day) to either 0.3 and 1 mg/kg 17- estradiol dipropionate (EP), 10 and 50 mg/kg bisphenol A (BPA), 10 and 50 mg/kg nonylphenol (NP), 30 and 100 mg/kg di-isoheptyl phthalate (DIHP), 30 and 100 mg/kg di (2-ethylhexyl) phthalate (DEHP), 30 and 100 mg/kg di (2-ethylhexyl) adipate (DEHA), 5 and 50 mg/kg p,p -dichlorodiphenyl-dichloroethylene (DDE) and 1.6 and 16.6 mg/kg quercetin or solvent control. Fourteen hours later the mice were sacrificed and tissues including liver, pituitary, brain, testes and bone were isolated and frozen immediately at -80 ¿C. Maximal luciferase activity, normalized for protein, was induced by 1 mg/kg EP in the liver (5400-fold), while this was 2-times lower at 0.3 mg EP/kg. Several compounds that were estrogenic in vitro were not estrogenic in vivo. However, tissue specific modulation of luciferase expression was found for some compounds, especially BPA induced luciferase in the liver and kidneys. Nonylphenol slightly induced luciferase in the liver and kidneys. Relative few compounds were estrogenic in vivo. In vitro the studied compounds are at least 104 less estrogenic than E2, this might explain the relative small amount of estrogenic compounds in vivo, as relative low concentrations were tested compared to our in vitro study

AB - Transgenic reporter gene mice carrying a 3xERE-tataluc- insulated construct were exposed to compounds found to be estrogenic in vitro. Transgenic male mice, chosen for their relative low background levels of circulating estrogens, were fed a phyto-estrogen free diet. They were housed individually and exposed orally via custard (0.5 ml/day) to either 0.3 and 1 mg/kg 17- estradiol dipropionate (EP), 10 and 50 mg/kg bisphenol A (BPA), 10 and 50 mg/kg nonylphenol (NP), 30 and 100 mg/kg di-isoheptyl phthalate (DIHP), 30 and 100 mg/kg di (2-ethylhexyl) phthalate (DEHP), 30 and 100 mg/kg di (2-ethylhexyl) adipate (DEHA), 5 and 50 mg/kg p,p -dichlorodiphenyl-dichloroethylene (DDE) and 1.6 and 16.6 mg/kg quercetin or solvent control. Fourteen hours later the mice were sacrificed and tissues including liver, pituitary, brain, testes and bone were isolated and frozen immediately at -80 ¿C. Maximal luciferase activity, normalized for protein, was induced by 1 mg/kg EP in the liver (5400-fold), while this was 2-times lower at 0.3 mg EP/kg. Several compounds that were estrogenic in vitro were not estrogenic in vivo. However, tissue specific modulation of luciferase expression was found for some compounds, especially BPA induced luciferase in the liver and kidneys. Nonylphenol slightly induced luciferase in the liver and kidneys. Relative few compounds were estrogenic in vivo. In vitro the studied compounds are at least 104 less estrogenic than E2, this might explain the relative small amount of estrogenic compounds in vivo, as relative low concentrations were tested compared to our in vitro study

M3 - Abstract

VL - 161

SP - 174 (1)

BT - Abstracts of the Dutch toxicology days, 13th-14th June 2006

ER -

ter Veld MGR, van der Saag PT, Rietjens IMCM, Murk AJ. Selective estrogenicity in orally exposed transgenic male mice of compounds known to be estrogenic in vitro. In Abstracts of the Dutch toxicology days, 13th-14th June 2006. Vol. 161. 2006. p. 174 (1)