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

Thorpe, Karen L.; Hutchinson, Thomas H.; Hetheridge, Malcolm J.; Scholze, Martin; Sumpter, John P.; Tyler, Charles R.

doi:10.1021/es001767u

Cited by 249 publications

(145 citation statements)

References 32 publications

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“…Even though estrogenic chemicals tend to be present at low concentrations and exhibit weak activity individually, the potential exposure to mixtures of these chemicals suggests the possibility of additive and/or interactive effects, which could produce a significant combined response (Payne et al, 2000;Thorpe et al, 2001). In toxicology, depending on the presumed modes of action of the mixture's components, two concepts are used to predict the effects of mixtures: concentration addition (CA) and independent action (IA).…”

Section: Introductionmentioning

confidence: 99%

Interactions between estrogenic chemicals in binary mixtures investigated using vitellogenin induction and factorial analysis

2009

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a b s t r a c tConsiderable progress has been made in assessing the combined effects of chemicals, but the effect of mixtures remains one of the most daunting challenges in environmental toxicology. In this study, the effects of binary mixtures of estrogenic chemicals were investigated using plasma vitellogenin (VTG) induction in male adult Japanese medaka (Oryzias latipes) as the endpoint. We focused on whether or not the factorial design using rigorous statistical methods was appropriate for the identification of possible interactions. The estrogenic activities of 17b-estradiol (E2), 4-tert-nonylphenol (NP) and bisphenol A (BPA) were investigated in medaka following 14 d of exposure. Although all chemicals induced concentration-dependent increases in plasma VTG, a complete concentration-response curve was obtained only for E2, while partial curves were obtained for NP and BPA. Therefore, a 3Â3 factorial design was employed to identify both the individual and interactive effects. A significant difference in mean plasma VTG induction was found when any chemical was considered alone. However, no significant interactions between E2 and NP, E2 and BPA, and NP and BPA were demonstrated. These results suggest that these three model estrogenic chemicals share a common mechanism for inducing VTG synthesis, and that no interactions occur when they act in combination. We also demonstrated the ability of this experimental design to detect interactions between binary mixtures, which will allow the assessment of biological effects of more complex mixtures in future research.

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Section: Introductionmentioning

confidence: 99%

Interactions between estrogenic chemicals in binary mixtures investigated using vitellogenin induction and factorial analysis

2009

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“…NP has also been shown to behave as a weak estrogen in a variety of standard in vitro tests including proliferation assays using the breast cancer MCF-7 cell line (Soto et al 1995, Blom et al 1998, Laws et al 2000, gene expression (Arukwe et al 2000a(Arukwe et al , 2001, Thorpe et al 2001), and recombinant reporter gene assays (Sohoni & Sumpter 1998, Yoon et al 2000. Previous reports demonstrate that NP binds directly to the estrogen receptor (ER) and subsequently induces transcription of downstream genes regulated by this pathway (Celius et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Distinct expression and activity profiles of largemouth bass (Micropterus salmoides) estrogen receptors in response to estradiol and nonylphenol

Sabo‐Attwood

Blum

Kroll

et al. 2007

Journal of Molecular Endocrinology

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The estrogen receptor (ER) signaling cascade is a vulnerable target of exposure to environmental xenoestrogens, like nonylphenol (NP), which are causally associated with impaired health status. However, the impact of xenoestrogens on the individual receptor isotypes (a, ba, and bb) is not well understood. The goal of these studies was to determine the impact of NP on largemouth bass (Micropterus salmoides) ER isotype expression and activity. Here, we show that hepatic expression levels of three receptors are not equivalent in male largemouth bass exposed to NP by injection. Transcript levels of the ERa subtype were predominantly induced in concert with vitellogenin similarly to fish exposed to 17b-estradiol (E 2 ) as measured by quantitative real-time PCR. NP also induced circulating plasma levels of estrogen, which may contribute to overall activation of the ERs. To measure the activation of each receptor isotype by E 2 and NP, we employed reporter assays using an estrogen response element (ERE)-luciferase construct. Results from these studies show that ERa had the greatest activity following exposure to E 2 and NP. This activity was inhibited by the antagonists ICI 182 780 and ZM 189 154. Furthermore, both bb and ba subtypes depressed ERa activation, suggesting that the cellular composition of receptor isotypes may contribute to the overall actions of estrogen and estrogenic contaminants via the receptors. Results from these studies collectively reveal the differential response of fish ER isotypes in response to xenoestrogens.

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“…It was thus evident that of the two key biomarkers, vtg1 proved a robust indicator of mixture-induced effects. This goes along with studies using juvenile rainbow trout (Thorpe et al 2001), adult and embryonic fathead minnow (Brian et al 2005, Johns et al 2011 and juvenile zebrafish (Lin and Janz 2006). Theoretically, the joint effect of BPA + NP + OP (II) resulted in minimum additive response of the component chemicals.…”

Section: Responses Of 20dpfzf To Xenoestrogenic Mixtures (Ii)mentioning

confidence: 79%

“…This is due to biological effects with multiple components in an environmental mixture that may act unexpectedly regarding their combined capacity of impacts (Sumpter and Jobling 1995). Overall, estrogenic chemicals in mixtures may show a combination of effects in aquatic models (Thorpe et al 2001, Brian et al 2005, Lin and Janz 2006, Petersen and Tollefsen 2012.…”

Section: Exposure To Chemicals As Mixturementioning

confidence: 99%

Probing the xeno-oestrogenic impact of sediment cores contaminated by the pulp and paper industry: induction of aromatase cyp19a1b in late larval zebrafish

Sahoo

Oikari

2014

J Soils Sediments

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To assess xenoestrogenicity, the 20 days-post-fertilization zebrafish (20dpfZF) life-stage was experimentally exposed to known model chemicals as well as to environmentally contaminated samples. From a selection of key responsive genes, molecular responses associated with the steroidogenic impact (brain aromatase, cyp19a1b and vitellogenin isoform 1, vtg1) were used to assess the endocrinic modulation by xenoestrogenic samples. This work showed diverse in vivo responses by the 20dpfZF, from pure chemicals (bisphenol A, BPA; 17 -ethinylestradiol, EE2; nonylphenol, NP; octylphenol, OP), and their mixture combinations, and to industrially contaminated sediment samples. Gene expression analysis of cyp19a1b and vtg1 in exposed 20dpfZF showed the estrogenic potencies of chemicals in the order: EE2 > OP > BPA > NP. Transcriptional up-regulation of vtg1 in early juvenile fish exposed to mixtures (BPA + NP + OP), relative to individual concentrations, suggest in minimum the additive in vivo effect of a mixture of very low sublethal doses of single xenoestrogens. Complementary expression of cyp19a1b and vtg1 in 20dpfZF, exposed to artificially-spiked sediment with EE2 established the estrogenresponsiveness of the model. In contrast, the lack of simple estrogenic or antiestrogenic trait of correspondence in biomarker transcription was evident from exposure to two types of industrially contaminated sediments, suggesting common non-linearity of in vivo response by the model. The results also highlight the applicability of 20dpfZF in the assessment of remediation and monitoring of historically polluted sites. This study showed that the 20dpfZF addressed the regulatory requirement of a multi-purpose and cost-effective ecotoxicological model capable of in vivo genomic assessment of endocrineactive substances in aquatic samples.

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

Cited by 249 publications

References 32 publications

Interactions between estrogenic chemicals in binary mixtures investigated using vitellogenin induction and factorial analysis

Interactions between estrogenic chemicals in binary mixtures investigated using vitellogenin induction and factorial analysis

Distinct expression and activity profiles of largemouth bass (Micropterus salmoides) estrogen receptors in response to estradiol and nonylphenol

Probing the xeno-oestrogenic impact of sediment cores contaminated by the pulp and paper industry: induction of aromatase cyp19a1b in late larval zebrafish

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