The effects of the fungicides fenhexamid and myclobutanil on SH-SY5Y and U-251 MG human cell lines

David A. Nagel, Eric J. Hill, John O'Neil, Alexandra Mireur, Michael D. Coleman

Research output: Contribution to journalArticle

Abstract

Mixtures of pesticides in foodstuffs and the environment are ubiquitous in the developed world and although agents are usually exhaustively tested individually, the toxicological implications of pesticide mixtures are underreported. In this study, the effects of two fungicides, fenhexamid and myclobutanil were investigated individually and in combination on two human cell lines, SH-SY5Y neuronal cells and U-251 MG glial cells. After 48. h of incubation with increasing concentrations of pesticides ranging from 1 to 1000. μM, gene expression profiles were studied in addition to toxicity end points, including cell viability, mitochondrial depolarisation as well as cellular glutathione maintenance. There were no significant differences between the susceptibility of the two cell lines in terms of cell viability assessment or mitochondrial membrane potential, when agents were administered either individually or in combination. By contrast, in the presence of the fungicides, the SH-SY5Y cells showed significantly greater susceptibility to oxidative stress in terms of total thiol depletion in comparison with the astrocytic cells. Treatment with the two pesticides led to significant changes in the cell lines' expression of several genes which regulate cell cycle control and growth (RB1, TIMP1) as well as responses to DNA attrition (ATM and CDA25A) and control of apoptosis (FAS). There was no evidence in this study that the combination of fenhexamid and myclobutanil was significantly more toxic than individual exposure, although gene expression changes suggested there may be differences in the sub-lethal response of both cell lines to both individual and combined exposure.

LanguageEnglish
Pages968-976
Number of pages9
JournalEnvironmental Toxicology and Pharmacology
Volume38
Issue number3
Early online date16 Sep 2014
DOIs
Publication statusPublished - Nov 2014

Fingerprint

Fungicides
Pesticides
Cells
Cell Line
Cell Survival
Gene Expression
Mitochondrial Membrane Potential
Poisons
Gene expression
Cell Cycle Checkpoints
Transcriptome
Sulfhydryl Compounds
Neuroglia
Toxicology
Glutathione
Oxidative Stress
Maintenance
Apoptosis
Oxidative stress
Depolarization

Keywords

  • astrocytes
  • fungicides
  • human
  • mixture
  • neurons
  • toxicity

Cite this

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The effects of the fungicides fenhexamid and myclobutanil on SH-SY5Y and U-251 MG human cell lines. / Nagel, David A.; Hill, Eric J.; O'Neil, John; Mireur, Alexandra; Coleman, Michael D.

In: Environmental Toxicology and Pharmacology, Vol. 38, No. 3, 11.2014, p. 968-976.

Research output: Contribution to journalArticle

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AU - Coleman, Michael D.

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