The in vivo effect of combinations of octylphenol, butylbenzylphthalate and estradiol on liver estradiol receptor modulation and induction of zona radiata proteins in rainbow trout: no evidence of synergy

Knudsen, Frank Reier; Arukwe, Augustine; Pottinger, T.G.

doi:10.1016/s0269-7491(98)00127-4

“…The concentration additive behavior of NP with E2 in these experiments, however, together with the ability of NP to bind the ER (but not the AR) in rainbow trout liver and brain cells (21), suggests that the VTG response induced by NP is mediated via the ER alone. This may also be true for the related alkylphenolic chemical, octylphenol, which has been shown to act in an additive manner with E2, in inducing VTG synthesis in rainbow trout (22).…”

Section: Resultsmentioning

confidence: 95%

Assessing the Biological Potency of Binary Mixtures of Environmental Estrogens using Vitellogenin Induction in Juvenile Rainbow Trout (Oncorhynchus mykiss)

Thorpe

¹

,

Hutchinson

²

,

Hetheridge

³

et al. 2001

Environ. Sci. Technol.

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Experiments were conducted to assess the in vivo potency of binary mixtures of estrogenic chemicals using plasma vitellogenin (VTG) concentrations in juvenile rainbow trout (Oncorhynchus mykiss) as the endpoint. The estrogenic potencies of estradiol-17beta (E2), 4-tertnonylphenol (NP), and methoxychlor (MXC) were determined following 14 day exposures to the individual chemicals and binary mixtures of these chemicals. E2, NP, and MXC all induced concentration dependent increases in plasma VTG, with lowest observed effect concentrations of 4.7 and 7.9 ng L(-1) for E2, 6.1 and 6.4 microg L(-1) for NP, and 4.4 and 6.5 microg L(-1) for MXC. Concentration-response curves for fixed ratio binary mixtures of E2 and NP (1:1000), E2 and MXC (1:1000), and NP and MXC (1:1) were compared to those obtained for the individual chemicals, using the model of concentration addition. Mixtures of E2 and NP were additive at the concentrations tested, but mixtures of E2 and MXC were less than additive. This suggests that while NP probably acts via the same mechanism as E2 in inducing VTG synthesis, MXC may be acting via a different mechanism(s), possibly as a result of its conversion to HPTE which is an estrogen receptor alpha agonist and an estrogen receptor beta antagonist. It was not possible to determine whether mixtures of MXC and NP were additive using VTG induction, because the toxicity of MXC restricted the effect range forwhich the expected response curve forthe binary mixture could be calculated. The data presented illustrate that the model of concentration addition can accurately predict effects on VTG induction, where we know that both chemicals act via the same mechanism in mediating a vitellogenic response.

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“…In most cases, rodent uterotrophic assays are used [12,13]. Besides mammals, organisms including fish and amphibians have been used as models for detection of estrogen receptor‐mediated toxicities [14,15]. In the latter case, the egg yolk protein vitellogenin was used as a biomarker because the production of vitellogenin is increased upon exposure to estrogenic chemicals [15,16].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of estrogenic activity of phthalate esters by gene expression profiling using a focused microarray (estrarray^®)

Parveen

¹

,

Inoue²,

Ise³

et al. 2008

Enviro Toxic and Chemistry

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Phthalates are used industrially as plasticizers and are known to contaminate natural environments, mostly as di-ester or mono-ester complexes. Because they are structurally similar to natural estrogens, they could act as endocrine disruptors. Here, we used a DNA microarray containing estrogen responsive genes (EstrArray) to examine gene expression profiles in MCF-7 cells treated with 10 microM butylbenzyl phthalate (BBP), dibutyl phthalate (DBP), diethyl phthalate (DEP), and diisopropyl phthalate (DIP) along with the natural estrogen 17beta-estradiol ([E(2)], 10 nM). The profiles for phthalate esters and E(2) were examined by correlation analysis using correlation coefficients (r-values) and cluster analysis. We found that BBP showed the highest correlation with E(2) (r = 0.85), and DEP and DIP showed moderate r-values (r = 0.52 and r = 0.49, respectively). Dibutyl phthalate exhibited the lowest (but still significant) correlation with E(2) (r = 0.36). Furthermore, among the pairs of chemicals, DEP-DIP and DIP-DBP showed very high correlations (r = 0.90 and r = 0.80, respectively), and the other pairs showed moderate relationships, which reflected how structurally close they are to each other. The analysis of six functional groups of genes (enzymes, signaling, proliferation, transcription, transport, and others) indicated that the genes belonging to the enzyme, transcription, and other functional groups showed common responses to phthalate esters and E(2). Although the effect of BBP was similar to that of E(2), the other phthalate esters showed different types of effects. These results indicate that the structure of estrogenic chemicals is strongly related to their estrogenic activity and can be evaluated by appropriate grouping of the responsive genes by focused microarray analysis.

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“…In most cases, rodent uterotrophic assays are used [12,13]. Besides mammals, organisms including fish and amphibians have been used as models for detection of estrogen receptor-mediated toxicities [14,15]. In the latter case, the egg yolk protein vitellogenin was used as a biomarker because the production of vitellogenin is increased upon exposure to estrogenic chemicals [15,16].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Estrogenic Activity of Phthalate Esters by Gene Expression Profiling Using a Focused Microarray (Estrarray®)

Parveen

¹

,

Inoue²,

Ise³

et al. 2007

Environ Toxicol Chem

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Phthalates are used industrially as plasticizers and are known to contaminate natural environments, mostly as di-ester or mono-ester complexes. Because they are structurally similar to natural estrogens, they could act as endocrine disruptors. Here, we used a DNA microarray containing estrogen responsive genes (EstrArray) to examine gene expression profiles in MCF-7 cells treated with 10 microM butylbenzyl phthalate (BBP), dibutyl phthalate (DBP), diethyl phthalate (DEP), and diisopropyl phthalate (DIP) along with the natural estrogen 17beta-estradiol ([E(2)], 10 nM). The profiles for phthalate esters and E(2) were examined by correlation analysis using correlation coefficients (r-values) and cluster analysis. We found that BBP showed the highest correlation with E(2) (r = 0.85), and DEP and DIP showed moderate r-values (r = 0.52 and r = 0.49, respectively). Dibutyl phthalate exhibited the lowest (but still significant) correlation with E(2) (r = 0.36). Furthermore, among the pairs of chemicals, DEP-DIP and DIP-DBP showed very high correlations (r = 0.90 and r = 0.80, respectively), and the other pairs showed moderate relationships, which reflected how structurally close they are to each other. The analysis of six functional groups of genes (enzymes, signaling, proliferation, transcription, transport, and others) indicated that the genes belonging to the enzyme, transcription, and other functional groups showed common responses to phthalate esters and E(2). Although the effect of BBP was similar to that of E(2), the other phthalate esters showed different types of effects. These results indicate that the structure of estrogenic chemicals is strongly related to their estrogenic activity and can be evaluated by appropriate grouping of the responsive genes by focused microarray analysis.

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The in vivo effect of combinations of octylphenol, butylbenzylphthalate and estradiol on liver estradiol receptor modulation and induction of zona radiata proteins in rainbow trout: no evidence of synergy

Cited by 19 publications

References 38 publications

Assessing the Biological Potency of Binary Mixtures of Environmental Estrogens using Vitellogenin Induction in Juvenile Rainbow Trout (Oncorhynchus mykiss)

Assessing the Biological Potency of Binary Mixtures of Environmental Estrogens using Vitellogenin Induction in Juvenile Rainbow Trout (Oncorhynchus mykiss)

Evaluation of estrogenic activity of phthalate esters by gene expression profiling using a focused microarray (estrarray^®)

Evaluation of Estrogenic Activity of Phthalate Esters by Gene Expression Profiling Using a Focused Microarray (Estrarray®)

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The in vivo effect of combinations of octylphenol, butylbenzylphthalate and estradiol on liver estradiol receptor modulation and induction of zona radiata proteins in rainbow trout: no evidence of synergy

Cited by 19 publications

References 38 publications

Assessing the Biological Potency of Binary Mixtures of Environmental Estrogens using Vitellogenin Induction in Juvenile Rainbow Trout (Oncorhynchus mykiss)

Assessing the Biological Potency of Binary Mixtures of Environmental Estrogens using Vitellogenin Induction in Juvenile Rainbow Trout (Oncorhynchus mykiss)

Evaluation of estrogenic activity of phthalate esters by gene expression profiling using a focused microarray (estrarray®)

Evaluation of Estrogenic Activity of Phthalate Esters by Gene Expression Profiling Using a Focused Microarray (Estrarray®)

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Evaluation of estrogenic activity of phthalate esters by gene expression profiling using a focused microarray (estrarray^®)