Food-associated estrogenic compounds induce estrogen receptor-mediated luciferase gene expression in transgenic male mice

Autor: Marcel G.R. ter Veld, J.H.J. van den Berg, Paul T. van der Saag, Albertinka J. Murk, Ivonne M.C.M. Rietjens, E. Zawadzka
Přispěvatelé: Hubrecht Institute for Developmental Biology and Stem Cell Research
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Male
Estrogen receptor
Administration
Oral
sprague-dawley rats
Endocrine Disruptors
Toxicology
in-vivo
chemistry.chemical_compound
Mice
Genes
Reporter
Luciferases
Chemistry
er-alpha
Phthalate
General Medicine
vitro
Wageningen Marine Research
Dose–response relationship
Liver
Receptors
Estrogen
Quercetin
Injections
Intraperitoneal
hormones
hormone substitutes
and hormone antagonists
p-nonylphenol
medicine.medical_specialty
endocrine system
phthalate-esters
assays
Food Contamination
Mice
Transgenic
reporter male-mice
Gene Expression Regulation
Enzymologic
Phenols
In vivo
Internal medicine
Diethylhexyl Phthalate
medicine
Animals
Benzhydryl compounds
Estrogens
Non-Steroidal
Benzhydryl Compounds
Toxicologie
VLAG
Dose-Response Relationship
Drug
urogenital system
Nonylphenol
Endocrinology
bisphenol-a
Food Additives
beta
Estrogen receptor alpha
Zdroj: Chemico-Biological Interactions, 174(2), 126-133. Elsevier Ireland Ltd
Chemico-Biological Interactions, 174(2), 126-133
Chemico-Biological Interactions 174 (2008) 2
ISSN: 0009-2797
DOI: 10.1016/j.cbi.2008.03.019
Popis: The present paper aims at clarifying to what extent seven food-associated compounds, shown before to be estrogenic in vitro, can induce estrogenic effects in male mice with an estrogen receptor (ER)-mediated luciferase (luc) reporter gene system. The luc induction was determined in different tissues 8 h after dosing the ER-luc male mice intraperitoneally (IP) or 14 h after oral dosing. Estradiol-propionate (EP) was used as a positive control at 0.3 and 1 mg/kg bodyweight (bw), DMSO as solvent control. The food-associated estrogenic compounds tested at non-toxic doses were bisphenol A (BPA) and nonylphenol (NP) (both at 10 and 50 mg/kg bw), dichlorodiphenyldichloroethylene (p,p¿-DDE; at 5 and 25 mg/kg bw), quercetin (at 1.66 and 16.6 mg/kg bw), di-isoheptyl phthalate (DIHP), di-(2-ethylhexyl) phthalate (DEHP) and di-(2-ethylhexyl) adipate (DEHA) all at 30 and 100 mg/kg bw. In general IP dosing resulted in higher luc inductions than oral dosing. EP induced luc activity in the liver in a statistically significant dose-related way with the highest induction of all compounds tested which was 20,000 times higher than the induction by the DMSO-control. NP, DDE, DEHA and DIHP did not induce luc activity in any of the tissues tested. BPA induced luc in the liver up to 420 times via both exposure routes. BPA, DEHP and quercetin induced luc activity in the liver after oral exposure. BPA (50 mg/kg bw IP) also induced luc activity in the testis, kidneys and tibia. The current study reveals that biomarker-responses in ER-luc male mice occur after a single oral exposure to food-associated estrogenic model compounds at exposure levels 10 to 104 times higher than the established TDI's for some of these compounds. Given the facts that (i) the present study did not include chronic exposure and that (ii) simultaneous exposure to multiple estrogenic compounds may be a realistic exposure scenario, it remains to be seen whether this margin is sufficiently high
Databáze: OpenAIRE
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