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Developmental Toxicology of Metal Mixtures in Drosophila: Unique Properties of Potency and Interactions of Mercury Isoforms
- Source :
- International Journal of Molecular Sciences, Volume 22, Issue 22, International Journal of Molecular Sciences, Vol 22, Iss 12131, p 12131 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- 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 (HgCl2), lead acetate (Pb), and sodium arsenite (As). To probe these differences, we used the Drosophila 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 HgCl2. Our results highlight a unique developmental window and toxicokinetic properties where MeHg acts with specificity relative to HgCl2, 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 HgCl2.
- Subjects :
- mercury
Sodium arsenite
QH301-705.5
Morphogenesis
Developmental toxicity
Catalysis
Inorganic Chemistry
chemistry.chemical_compound
toxicokinetics
Toxicokinetics
Biology (General)
Physical and Theoretical Chemistry
heavy metals
QD1-999
Molecular Biology
Methylmercury
Spectroscopy
lead
metamorphosis
Chemistry
Organic Chemistry
arsenic
pupariation
General Medicine
Computer Science Applications
mixture
eclosion
Drosophila
Biochemistry
Lead acetate
Toxicity
Pupariation
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....ba9a7e489b1e72cb7c7c58f1c6ae43f4