Developmental Toxicology of Metal Mixtures in <i>Drosophila</i>: Unique Properties of Potency and Interactions of Mercury Isoforms

Mercury ranks third on the U.S. Agency of Toxic Substances and Disease Registry priority list of hazardous substances, behind only arsenic and lead. We have undertaken uncovering the mechanisms underlying the developmental toxicity of methylmercury (MeHg), inorganic mercury (HgCl<sub>2</sub...

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Autores principales:	Catherine R. Beamish, Tanzy M. Love, Matthew D. Rand
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	heavy metals mixture <i>Drosophila</i> mercury arsenic lead Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/707cd68597e348d29f2da67d8ae0bf2a
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spelling	oai:doaj.org-article:707cd68597e348d29f2da67d8ae0bf2a2021-11-25T17:53:40ZDevelopmental Toxicology of Metal Mixtures in <i>Drosophila</i>: Unique Properties of Potency and Interactions of Mercury Isoforms10.3390/ijms2222121311422-00671661-6596https://doaj.org/article/707cd68597e348d29f2da67d8ae0bf2a2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12131https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Mercury ranks third on the U.S. Agency of Toxic Substances and Disease Registry priority list of hazardous substances, behind only arsenic and lead. We have undertaken uncovering the mechanisms underlying the developmental toxicity of methylmercury (MeHg), inorganic mercury (HgCl<sub>2</sub>), lead acetate (Pb), and sodium arsenite (As). To probe these differences, we used the <i>Drosophila</i> model, taking advantage of three developmental transitions—pupariation, metamorphosis, and eclosion—to differentiate potentially unique windows of toxicity. We elaborated dose response profiles for each individual metal administered in food and accounted for internal body burden, also extending analyses to evaluate combinatorial metal mixture effects. We observed all four metals producing larval lethality and delayed pupariation, with MeHg being most potent. Compared to other metals, MeHg’s potency is caused by a higher body burden with respect to dose. MeHg uniquely caused dose-dependent failure in eclosion that was unexpectedly rescued by titrating in HgCl<sub>2</sub>. Our results highlight a unique developmental window and toxicokinetic properties where MeHg acts with specificity relative to HgCl<sub>2</sub>, Pb, and As. These findings will serve to refine future studies aimed at revealing tissue morphogenesis events and cell signaling pathways, potentially conserved in higher organisms, that selectively mediate MeHg toxicity and its antagonism by HgCl<sub>2</sub>.Catherine R. BeamishTanzy M. LoveMatthew D. RandMDPI AGarticleheavy metalsmixture<i>Drosophila</i>mercuryarsenicleadBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12131, p 12131 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	heavy metals mixture <i>Drosophila</i> mercury arsenic lead Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	heavy metals mixture <i>Drosophila</i> mercury arsenic lead Biology (General) QH301-705.5 Chemistry QD1-999 Catherine R. Beamish Tanzy M. Love Matthew D. Rand Developmental Toxicology of Metal Mixtures in <i>Drosophila</i>: Unique Properties of Potency and Interactions of Mercury Isoforms
description	Mercury ranks third on the U.S. Agency of Toxic Substances and Disease Registry priority list of hazardous substances, behind only arsenic and lead. We have undertaken uncovering the mechanisms underlying the developmental toxicity of methylmercury (MeHg), inorganic mercury (HgCl<sub>2</sub>), lead acetate (Pb), and sodium arsenite (As). To probe these differences, we used the <i>Drosophila</i> model, taking advantage of three developmental transitions—pupariation, metamorphosis, and eclosion—to differentiate potentially unique windows of toxicity. We elaborated dose response profiles for each individual metal administered in food and accounted for internal body burden, also extending analyses to evaluate combinatorial metal mixture effects. We observed all four metals producing larval lethality and delayed pupariation, with MeHg being most potent. Compared to other metals, MeHg’s potency is caused by a higher body burden with respect to dose. MeHg uniquely caused dose-dependent failure in eclosion that was unexpectedly rescued by titrating in HgCl<sub>2</sub>. Our results highlight a unique developmental window and toxicokinetic properties where MeHg acts with specificity relative to HgCl<sub>2</sub>, Pb, and As. These findings will serve to refine future studies aimed at revealing tissue morphogenesis events and cell signaling pathways, potentially conserved in higher organisms, that selectively mediate MeHg toxicity and its antagonism by HgCl<sub>2</sub>.
format	article
author	Catherine R. Beamish Tanzy M. Love Matthew D. Rand
author_facet	Catherine R. Beamish Tanzy M. Love Matthew D. Rand
author_sort	Catherine R. Beamish
title	Developmental Toxicology of Metal Mixtures in <i>Drosophila</i>: Unique Properties of Potency and Interactions of Mercury Isoforms
title_short	Developmental Toxicology of Metal Mixtures in <i>Drosophila</i>: Unique Properties of Potency and Interactions of Mercury Isoforms
title_full	Developmental Toxicology of Metal Mixtures in <i>Drosophila</i>: Unique Properties of Potency and Interactions of Mercury Isoforms
title_fullStr	Developmental Toxicology of Metal Mixtures in <i>Drosophila</i>: Unique Properties of Potency and Interactions of Mercury Isoforms
title_full_unstemmed	Developmental Toxicology of Metal Mixtures in <i>Drosophila</i>: Unique Properties of Potency and Interactions of Mercury Isoforms
title_sort	developmental toxicology of metal mixtures in <i>drosophila</i>: unique properties of potency and interactions of mercury isoforms
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/707cd68597e348d29f2da67d8ae0bf2a
work_keys_str_mv	AT catherinerbeamish developmentaltoxicologyofmetalmixturesinidrosophilaiuniquepropertiesofpotencyandinteractionsofmercuryisoforms AT tanzymlove developmentaltoxicologyofmetalmixturesinidrosophilaiuniquepropertiesofpotencyandinteractionsofmercuryisoforms AT matthewdrand developmentaltoxicologyofmetalmixturesinidrosophilaiuniquepropertiesofpotencyandinteractionsofmercuryisoforms
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Developmental Toxicology of Metal Mixtures in <i>Drosophila</i>: Unique Properties of Potency and Interactions of Mercury Isoforms

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