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

Roger M Pallares1, Dahlia D An1, Solène Hébert1

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This study reveals key genes and proteins involved in early lanthanide toxicity using yeast. Findings on lanthanum and praseodymium toxicity offer insights into human health effects and potential treatments.

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Area of Science:

  • Environmental Toxicology
  • Genomics
  • Biochemistry

Background:

  • Lanthanides are crucial in various applications but their toxicity is not fully understood.
  • Previous genomic studies characterized mid and late lanthanides, but early lanthanides remained unstudied.
  • Understanding early lanthanide toxicity is vital for risk assessment and safety.

Purpose of the Study:

  • To elucidate the toxicological mechanisms of early lanthanides, specifically lanthanum and praseodymium.
  • To identify genes and proteins involved in the cellular response to these metals.
  • To explore potential human health implications of early lanthanide exposure.

Main Methods:

  • Utilized a genome-wide toxicogenomic approach in *Saccharomyces cerevisiae* (yeast) as a model organism.
  • Performed functional analysis and protein-protein interaction network analysis.
  • Investigated the dysregulation of key enzymes by early lanthanides.

Main Results:

  • Identified specific genes and proteins mediating yeast's response to lanthanum and praseodymium toxicity.
  • Highlighted key enzymes whose function is disrupted by early lanthanides, leading to cytotoxicity.
  • Found that several identified genes/proteins have human orthologs, suggesting conserved toxicity pathways.

Conclusions:

  • This research fills a critical knowledge gap regarding early lanthanide toxicology.
  • The identified molecular players provide a basis for understanding human responses to lanthanide exposure.
  • Findings may inform the development of strategies to mitigate lanthanide-induced toxicity.