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.
Highlights
Exposures to toxic metals commonly occur under long-term low-level conditions, and most of these exposures occur as a combination of multiple metals [1]
Larvae reared on various concentrations of MeHg food showed dose-dependent delays in development as shown by the right shift of the time to pupariation curves and quantified by pupariation time (PT, Figure 1a,d)
We highlighted the exceptional potency of MeHg and its ability to uniquely inhibit eclosion failure
Summary
Exposures to toxic metals commonly occur under long-term low-level conditions, and most of these exposures occur as a combination of multiple metals [1]. At the top of The Agency for Toxic Substances and Disease Registry’s priority list of hazardous substances are the metals arsenic (As), lead (Pb) and mercury (Hg), in that order based on their prevalence in the environment and threat to human health [10]. These metals all share the ability to cause neurotoxicity [11,12,13,14,15] and cause the most harm during development [16]. Only in limited cases has the model been leveraged to investigate metal mixtures in a systemic manner [26]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
