The toxicity of hexanedione isomers in neural and astrocytic cell lines

Elizabeth K. Woehrling*, Thomas R. Zilz, Michael D. Coleman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The metabolite 2,5-hexanedione (HD) is the cause of neurotoxicity linked with chronic n-hexane exposure. Acute exposure to high levels of 2,5-HD, have also shown toxic effects in neuronal cells and non-neuronal cells. Isomers of 2,5-HD, 2,3- and 3,4-HD, added to foodstuffs, are reported to be non-toxic. The acute cytotoxic effects of 2,5-, 2,3- and 3,4-HD were evaluated in neural (NT2.N, SK-N-SH), astrocytic (CCF-STTG1) and non-neural (NT2.D1) cell lines. All the cell lines were highly resistant to 2,5-HD (34-426 mM) at 4-h exposure, although sensitivity was greatest with NT2.D1, then SK-N-SH, NT2.N and finally the CCF-STTG1 line. At 24-h exposure, cell vulnerability increased 5-10-fold. The NT2.D1 cells were again the most sensitive, followed by NT2.N, SK-N-SH and then the CCF-STTG1 cells. 2,3- and 3,4-HD (8-84 mM), were significantly more toxic towards all four cell lines compared with 2,5-HD, after 4-h exposure. After 24-h exposure there was a 12-fold increase in inhibition of MTT turnover in the SK-N-SH cells and a 4-fold increase in the CCF-STTG1 cells, compared with 2,5-HD exposure. 2,3- and 3,4-HD, were significantly less toxic to the NT2.N cells than the SK-N-SH cells after 24-h exposure to the compounds, demonstrating a differing toxin vulnerability between these neural and neuroblastoma cell lines. This study indicates that these non-neuronal and neuronal cells are acutely resistant to 2,5-HD cytotoxicity, whilst the previously unreported sensitivity of all four cell lines to the 2,3- and 3,4- isomers of HD to has been shown to be significantly greater than that of 2,5-HD. © 2006 Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)249-254
Number of pages6
JournalEnvironmental Toxicology and Pharmacology
Issue number3
Early online date23 Feb 2006
Publication statusPublished - Nov 2006


  • astrocytic
  • hexanedione
  • neural
  • NT2.N
  • SK-N-SH


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