Related Experiment Video
Updated: May 14, 2026
Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
Published on: June 9, 2017
Differentially expressed genes and pathways induced by organophosphates in human neuroblastoma cells
Tianwei Li1, Hongtao Zhao, Guo-Chiuan Hung
1Tissue Safety Laboratory Program, Center for Biologics Evaluation and Research, Food and Drug Administration, NIH Building 29B, 29 Lincoln Drive, Bethesda, MD 20892, USA.
Abstract:
Organophosphates (OPs) are toxic chemicals commonly used as pesticides and herbicides. Some OPs are highly toxic to humans and have been used in warfare and terrorist attacks. In order to elucidate the molecular mechanisms of injury caused by OPs, the differentially expressed genes were analyzed in human SK-N-SH neuroblastoma cells induced by three OPs. The SK-N-SH cells were treated with one of the three OPs, chlorpyrifos, dichlorvos or methamidophos at LC20 (high-dose), the concentration causing 20% cell death, as well as 1/20 of LC20 (low-dose), a sub-lethal concentration with no detectable cell death, for 24 h. The genome-wide gene changes were identified by Agilent Microarray System, and analyzed by microarray analysis tools. The analysis revealed neuroblastoma cells treated with the high doses of all three OPs markedly activated cell apoptosis and inhibited cell growth and proliferation genes, which would most likely lead to the process of cell death. Interestingly, the analysis also revealed significant decrease in expressions of many genes in a specific spliceosome pathway in cells treated with the low doses of all three different OPs. The change of spliceosome pathway may represent an important mechanism of injury in neuronal cells exposed to low doses of various OPs. In addition to unraveling a potentially different form of OP pathogenesis, this finding could provide a new diagnostic marker in assessing OP-associated injury in cells or tissues. In addition, these results could also contribute to the development of new prevention and/or therapeutic regimens against OP toxicity.
Insights
Organophosphate pesticides, when studied in neuroblastoma cells, showed high doses induced cell death. Low doses significantly altered spliceosome pathways, suggesting a novel mechanism for organophosphate (OP) neurotoxicity.
Area of Science:
- Toxicology
- Molecular Biology
- Neuroscience
Background:
- Organophosphates (OPs) are widely used pesticides and herbicides with significant human toxicity.
- OPs have been employed as chemical warfare agents, necessitating research into their mechanisms of injury.
- Understanding OP molecular pathogenesis is crucial for developing countermeasures.
Purpose of the Study:
- To investigate the molecular mechanisms of injury induced by three different organophosphates (chlorpyrifos, dichlorvos, methamidophos) in human neuroblastoma cells.
- To identify differentially expressed genes and pathways affected by both high and low doses of OPs.
- To explore potential diagnostic markers and therapeutic targets for OP toxicity.
Main Methods:
- Human SK-N-SH neuroblastoma cells were exposed to chlorpyrifos, dichlorvos, or methamidophos at high (LC20) and low (LC20/20) doses for 24 hours.
- Genome-wide gene expression changes were analyzed using the Agilent Microarray System.
- Microarray data were analyzed to identify significant gene expression alterations and affected pathways.
Main Results:
- High doses of all three OPs significantly activated apoptosis and inhibited cell growth and proliferation genes.
- Low, sub-lethal doses of all three OPs markedly decreased the expression of genes within a specific spliceosome pathway.
- This spliceosome pathway alteration represents a potential novel mechanism of neuronal injury from low-dose OP exposure.
Conclusions:
- Organophosphate exposure at high doses leads to cell death through apoptosis and growth inhibition.
- Low-dose organophosphate exposure significantly impacts the spliceosome pathway, indicating a distinct mechanism of neurotoxicity.
- Alterations in the spliceosome pathway may serve as a diagnostic marker for OP-associated neuronal injury and inform new therapeutic strategies.
