Ireland, NicholasMiller, LydiaCaito, Samuel2023-11-132023-11-132023-04-20https://dspace.husson.edu/handle/20.500.14298/58Lanthanide series elements are transition metals that are used in a variety of electronics, including superconductors, electronic polishers, hybrid car components, and rechargeable batteries, as well as in fertilizers, antimicrobials, contrast agents for medical imaging and diesel fuel additives. Lanthanides are also present in electronic waste and are released during electronic cigarette smoking. Levels of lanthanides have risen significantly in both industrial areas and environmentally. While we are starting to recognize health effects of lanthanide exposure, it is currently unknown how lanthanide metals enter cells. If we are to understand their toxicokinetics in the human body, it is imperative to determine mechanisms by which lanthanides are distributed. We hypothesized that endogenous divalent metal transporters (DMTs) are responsible for lanthanide entry into cells, and that genetic ablation of DMT transporters in Caenorhabditis elegans would protect the worms from lanthanide-induced toxicity. In this study, we performed a competitive inhibition survival assay by pretreating wildtype worms with nonlethal doses of metals that enter cells through a variety of mechanisms, then treating the worms with increasing concentrations of lanthanum (La). Lethality was assessed 48 hours post exposure. Worms treated with either manganese or iron, metals that enter cells via DMTs, shifted the La dose-response survival curve to the right, suggesting La was competing for the same transporter as iron or manganese. However worms pretreated with zinc, magnesium, or chromium could not block lanthanum-mediated lethality. These data suggest that DMTs are responsible for lanthanides to enter cells. We then treated transgenic worms that lacked DMT homologs smf-1, smf-2, or smf-3, with increasing concentrations of La or ytterbium (Yb). Knock out of either of the smf genes shifted the dose-response curve for La or Yb to the right, showing protection. These results suggest that DMTs are important mediators for lanthanide series elements to enter eukaryotic cells.en-USAbstract