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

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.