title: The effects of nonyl phenoxypolyethoxyl ethanol on cell damage pathway gene expression in SK-NSH cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Samel
authors.initials: S
authors.lastname: Park
authors.affiliation: Pesticide Intoxication Institute, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Il-woong
authors.initials: IW
authors.lastname: Hwang
authors.affiliation: Pesticide Intoxication Institute, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Jin-sheon
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Hyo-chul
authors.initials: HC
authors.lastname: Kang
authors.affiliation: Biostatistical Consulting Unit, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Su-Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Hyo-wook
authors.initials: HW
authors.lastname: Gil
authors.affiliation: Department of Microbiology, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Ho-yeon
authors.initials: HY
authors.lastname: Song
authors.affiliation: Department of Internal Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea.
authors.forename: Sae-yong
authors.initials: SY
authors.lastname: Hong
mesh_terms: D000368:Aged; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018816:Genes, cdc; D050957:HSP110 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000506:poisoning; D009336:Necrosis; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017137:Nonoxynol / Q000737:chemistry / Q000633:toxicity*; D010575:Pesticides / Q000737:chemistry / Q000506:poisoning*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry / Q000633:toxicity*
chemical_list: D050957:HSP110 Heat-Shock Proteins; C121993:HSPA4 protein, human; D010575:Pesticides; D012333:RNA, Messenger; D013501:Surface-Active Agents; D017137:Nonoxynol; D007294:Inositol; C003749:validamycins
keywords: Cell damage pathways; Gene expression; Nonyl phenoxypolyethoxylethanol; Surface-active agents; Validamycins