Identifying Toxicity Mechanisms Associated with Early Lanthanide Exposure through Multidimensional Genome-Wide Screening

Abstract

Lanthanides are a series of elements essential to a wide range of applications, from clean energy production to healthcare. Despite their presence in multiple products and technologies, their toxicological characteristics have been only partly studied. Recently, our group has employed a genomic approach to extensively characterize the toxicity mechanisms of lanthanides. Even though we identified substantially different behaviors for mid and late lanthanides, the toxicological profiles of early lanthanides remained elusive. Here, we overcome this gap by describing a multidimensional genome-wide toxicogenomic study for two early lanthanides, namely, lanthanum and praseodymium. We used Saccharomyces cerevisiae as a model system since its genome shares many biological pathways with humans. By performing functional analysis and protein–protein interaction network analysis, we identified the main genes and proteins that participate in the yeast response to counter metal harmful effects. Moreover, our analysis also highlighted key enzymes that are dysregulated by early lanthanides, inducing cytotoxicity. Several of these genes and proteins have human orthologues, indicating that they may also participate in the human response against the metals. By highlighting the key genes and proteins in lanthanide-induced toxicity, this work may contribute to the development of new prophylactic and therapeutic strategies against lanthanide harmful exposures.

Ytterbium (III) Fluoride in Dental Materials

“…Lastly, the concerns that have been expressed about the toxicity of YbF 3 [11,18] do not seem to be supported by the published evidence on the effect of trace amounts of the substance on humans [12,54]. However, given the use described in this review in dental materials, this lack of clarity about toxicity is concerning, and further studies on this topic are clearly desirable as well.…”

“…This means that lanthanides, including ytterbium, may displace these ions in certain cellular functions, and compete with them for active binding sites in enzymes and other important bio-molecules [17]. Hence, lanthanides may impair the biological function of these substances, interfering with metabolism and showing toxicity [18], at least to an extent.…”

Development of radiopharmaceuticals for targeted alpha therapy: Where do we stand?

“…Free radioisotopes and metals, particularly f-block elements, have high binding affinities for biological receptors (30,31), resulting in their endogenous chelation and subsequent deposition in tissues (32,33). Internal contamination with radiometals (and their decay products) cause metal-and radiotoxicity, as multiple biological processes get disrupted (34)(35)(36)(37)(38)(39). Therefore, minimizing daughter release is a fundamental step to extend the use of targeted alpha therapy beyond metastatic non-responding patients (28).…”