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Korean J Intern Med. 2015 Nov;30(6):873-83. doi: 10.3904/kjim.2015.30.6.873. Epub 2015 Oct 30.

The effects of nonyl phenoxypolyethoxyl ethanol on cell damage pathway gene expression in SK-NSH cells.

Author information

1
Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
2
Pesticide Intoxication Institute, Soonchunhyang University College of Medicine, Cheonan, Korea.
3
Biostatistical Consulting Unit, Soonchunhyang University College of Medicine, Cheonan, Korea.
4
Department of Microbiology, Soonchunhyang University College of Medicine, Cheonan, Korea.

Abstract

BACKGROUND/AIMS:

Most pesticide formulations contain both chief and additive ingredients. But, the additives may not have been tested as thoroughly as the chief ingredients. The surfactant, nonyl phenoxypolyethoxylethanol (NP40), is an additive frequently present in pesticide formulations. We investigated the effects of NP40 and other constituents of a validamycin pesticide formulation on cell viability and on the expression of genes involved in cell damage pathways.

METHODS:

The effects of validamycin pesticide ingredients on cell viability and of NP40 on the mRNA expression of 80 genes involved in nine key cellular pathways were examined in the human neuroblastoma SK-N-SH cell line.

RESULTS:

The chemicals present in the validamycin pesticide formulation were cytotoxic to SK-N-SH cells and NP40 showed the greatest cytotoxicity. A range of gene expression changes were identified, with both up- and down-regulation of genes within the same pathway. However, all genes tested in the necrosis signaling pathway were down-regulated and all genes tested in the cell cycle checkpoint/arrest pathway were up-regulated. The median fold-change in gene expression was significantly higher in the cell cycle checkpoint/arrest pathway than in the hypoxia pathway category (p = 0.0064). The 70 kDa heat shock protein 4 gene, within the heat shock protein/unfolded protein response category, showed the highest individual increase in expression (26.1-fold).

CONCLUSIONS:

NP40 appeared to be particularly harmful, inducing gene expression changes that indicated genotoxicity, activation of the cell death (necrosis signaling) pathway, and induction of the 70 kDa heat shock protein 4 gene.

KEYWORDS:

Cell damage pathways; Gene expression; Nonyl phenoxypolyethoxylethanol; Surface-active agents; Validamycins

PMID:
26552463
PMCID:
PMC4642017
DOI:
10.3904/kjim.2015.30.6.873
[Indexed for MEDLINE]
Free PMC Article

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