Precision-cut tissue chips as an in vitro toxicology system

J. M. Catania, A. M. Pershing, A. J. Gandolfi

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Precision-cut tissue slices mimic specific organ toxicity because normal cellular heterogeneity and organ architecture are retained. To optimize the use of the smaller tissues of the mouse and to establish easy assays for tissue viability, a tissue chip based system was used to generate large numbers of samples from a single organ. Iodoacetamide (IAM) was used as a model toxicant and assays for intracellular potassium (normalized to DNA content) were used to establish viability and toxicant susceptibility. Thereafter, assays that were more rapid and specific were pursued. Lysates from tissues incubated in 6-carboxyfluorescein fluoresced proportionately to concentrations of IAM, indicating disruption of cellular membranes. Similarly, FURA-2, a probe applied to lysates to measure calcium levels, fluoresced proportionately to IAM dosage. Monobromobimane, a fluorescent sulfhydryl probe, displayed a decrease in fluorescent intensity at higher IAM challenge-a finding confirmed with an absorbance assay with Ellman's reagent. Importantly, the number of samples per organ/mouse was increased at least threefold and a significant time reduction per analysis was realized.

Original languageEnglish (US)
Pages (from-to)956-961
Number of pages6
JournalToxicology in Vitro
Volume21
Issue number5
DOIs
StatePublished - Aug 1 2007

Keywords

  • Fluorescent probes
  • In vitro toxicology
  • Precision-cut liver slices
  • Precision-cut tissue slices

ASJC Scopus subject areas

  • Toxicology

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