Korean J Intern Med.  2015 Nov;30(6):873-883. 10.3904/kjim.2015.30.6.873.

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

• Park S
• Hwang IW
• Kim JS
• Kang HC
• Park SY
• Gil HW
• Song HY
• Hong SY

• KMID: 2381592
• DOI: http://doi.org/10.3904/kjim.2015.30.6.873

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.

Keyword

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

MeSH Terms

Aged
Cell Cycle Checkpoints/drug effects/genetics
Cell Line, Tumor
Cell Survival/drug effects
Dose-Response Relationship, Drug
Female
Gene Expression Regulation/drug effects
Genes, cdc
HSP110 Heat-Shock Proteins/genetics/metabolism
Humans
Inositol/*analogs & derivatives/chemistry/poisoning
Necrosis
Neurons/*drug effects/metabolism/pathology
Nonoxynol/chemistry/*toxicity
Pesticides/chemistry/*poisoning
RNA, Messenger/metabolism
Signal Transduction/drug effects
Surface-Active Agents/chemistry/*toxicity
HSP110 Heat-Shock Proteins
Inositol
Nonoxynol
Pesticides
RNA, Messenger
Surface-Active Agents