Evidence for a differential translocation of actinides across human lung epithelial cell monolayer in vitro according to their physicochemical properties and the presence of a chelating agent

Toxicol In Vitro. 2021 Feb:70:105035. doi: 10.1016/j.tiv.2020.105035. Epub 2020 Oct 22.

Abstract

The epithelial cell plays a key role in the transfer of radionuclides from lungs to blood following pulmonary exposure. The present study was designed to evaluate the transfer across human lung epithelial cells of various actinides (plutonium, americium and uranium), the influence of the physicochemical properties of plutonium compounds and of the chelating agent diethylene triamine pentaacetic acid (DTPA). To address this question, Calu-3 cells grown in a bicameral culture system were used. The integrity of the epithelial barrier was evaluated by measuring transepithelial electrical resistance (TEER) and the passage of a fluorescent marker, lucifer yellow. Activity measurement in basal compartment following periodic collection of culture medium was made from 2 h to seven days. To facilitate data handling and analysis, the statistical tool STATBIODIS was used. The results indicate differences in transfer for the different elements, and according to Pu physicochemical properties. Though to various extents, the chelating agent DTPA always increased the transfer of Pu and Am across the epithelial cells, without altering the integrity of the epithelial barrier. This in vitro cell culture model, by mimicking translocation of actinides from lungs to blood, can represent a valuable tool to further understand the underlying mechanisms and properties controlling this process.

Keywords: Actinides; Chelating agent; Lung epithelial barrier; Translocation.

MeSH terms

  • Actinoid Series Elements / chemistry
  • Actinoid Series Elements / pharmacology*
  • Actinoid Series Elements / toxicity
  • Biological Transport / drug effects
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology*
  • Chelating Agents / toxicity
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Lung / cytology
  • Pentetic Acid / chemistry
  • Pentetic Acid / pharmacology*
  • Pentetic Acid / toxicity

Substances

  • Actinoid Series Elements
  • Chelating Agents
  • Pentetic Acid
  • L-Lactate Dehydrogenase