Short and long-term exposure of CNS cell lines to BPA-f a radiosensitizer for Boron Neutron Capture Therapy: Safety dose evaluation by a battery of cytotoxicity tests

U. De Simone, L. Manzo, C. Ferrari, J. Bakeine, C. Locatelli, T. Coccini

Research output: Contribution to journalArticle

Abstract

Despite the current clinical use of boronophenylalanine-fructose (BPA-f), as radiosensitizer, in BNCT application for brain tumors, still remains to be determined the safety dose of this agent. We evaluated the potential risk of primary BPA-f toxicity before neutronic irradiation at different concentrations (0-100μgBeq/ml) after short- and long-term exposure (4-48h and 7-10 days), using a battery of tests (i.e. MTT assay, calcein-AM/Propidium Iodide staining, clonogenic test) in CNS cell models (D384 and SH-SY5Y), and non-neuronal primary human fibroblasts (F26). MTT data showed: (i) no cytotoxic effects after short-term exposure (4h) to any of BPA-f concentrations tested in all cell models; (ii) dose- and time-dependent mitochondrial activity impairment in D384 and SH-SY5Y cells only (with 60% and 40% cell death in D384 and SH-SY5Y, respectively, after 48h exposure to BPA-f 100μgBeq/ml). By Calcein-AM/PI staining, BPA-f treatment was specific toward SH-SY5Y cells only: a dose-dependent cell density reduction was observed, with a more pronounced effect after 48h exposure (15-40% at doses ranging 20-100μgBeq/ml). Clonogenic data revealed dose-dependent decrease of cell proliferative capacity in all cell lines, still the SH-SY5Y cells were the most sensitive ones: the lowest dose (20μgBeq/ml) produced 90% cell decrease. These results indicate dose- and time-dependent cytotoxic effects of BPA-f, with CNS cells showing a lower tolerance compared to fibroblasts. Long-term exposure to BPA-f compromised the proliferative capacity regardless of cell model type (cell sensitivity being SH-SY5Y>D384>F26). In short-time exposure, BPA-f exhibits a safe dosage up to 40μgBeq/ml for the viability of CNS cell lines.

Original languageEnglish
Pages (from-to)84-90
Number of pages7
JournalNeuroToxicology
Volume35
Issue number1
DOIs
Publication statusPublished - Mar 2013

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Keywords

  • Boron delivery agent (boronophenylalanine-fructose - BPA-f)
  • Boron Neutron Capture Therapy (BNCT)
  • D384 cells, SH-SY5Y cells
  • In vitro cytotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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