Environmentally relevant levels of depleted uranium impacts dermal fibroblast proliferation, viability, metabolic activity, and scratch closure

Nathan Cruz, Robert Buscaglia, Matthew Salanga, Robert Kellar

Research output: Contribution to journalArticlepeer-review

Abstract

Uranium (U) is a heavy metal used in military and industrial settings, with a large portion being mined from the Southwest region of the United States. Uranium has uses in energy and military weaponry, but the mining process has released U into soil and surface waters that may pose threats to human and environmental health. The majority of literature regarding U’s human health concern focuses on outcomes based on unintentional ingestion or inhalation, and limited data are available about its influence via cutaneous contact. Utilizing skin dermis cells, we evaluated U’s topical chemotoxicity. Employing soluble depleted uranium (DU) in the form of uranyl nitrate (UN), we hypothesized that in vitro exposure of UN will have cytotoxic effects on primary dermal fibroblasts by affecting cell viability and metabolic activity and, further, may delay wound healing aspects via altering cell proliferation and migration. Using environmentally relevant levels of U found in water (0.1 µM to 100 µM [UN]; 23.8–23,800 ppb [U]), we quantified cellular mitosis and migration through growth curves and in vitro scratch assays. Cells were exposed from 24 h to 144 h for a time-course evaluation of UN chemical toxicity. The effects of UN were observed at concentrations above and below the Environmental Protection Agency threshold for safe exposure limits. UN exposure resulted in a dose-dependent decrease in the viable cell count; however, it produced an increase in metabolism when corrected for the viable cells present. Furthermore, cellular proliferation, population doubling, and percent closure was hindered at levels ≥10 µM UN. Therefore, inadvertent exposure may exacerbate pre-existing skin diseases in at-risk demographics, and additionally, it may substantially interfere in cutaneous tissue repair processes.

Original languageEnglish (US)
Article number211
JournalToxics
Volume9
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • Cellular respiration
  • Cytotoxicity
  • Dermis cell
  • Growth curve
  • Navajo nation
  • Scratch assay
  • Skin
  • Statistical modeling
  • Uranyl nitrate
  • Wound healing

ASJC Scopus subject areas

  • Toxicology
  • Chemical Health and Safety
  • Health, Toxicology and Mutagenesis

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