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Chlorpyrifos is an organophosphate and the cypermethrin is Type 2 pyrethroid insecticide that are frequently used for indoor and outdoor pest control. The combination of both chlorpyrifos and cypermethrin is commonly used to control pest and prolonged exposures of this combination results in chronic or persistent neurologic and teratogenic effects along with abortions and other reproductive failure. We have earlier reported that delay exposure to cypermethrin and chlorpyriphos results in lung injury, however, the molecular mechanism remains to be elucidated. The present study was designed to study differential transcriptional profiling to identify the candidate genes associated with lung injury after exposure to chlorpyriphos and/or cypermethrin in a mouse model. Swiss male albino mice (N=24) ageing 6-8 week were divided into one control group and three treatment groups (n=8each). Treatment group-І, ІІ and ІІІ were given orally chlorpyriphos (2.76 mg/kg), cypermethrin (2 mg/kg) and combination dissolved in corn oil for 90 days. Lung samples were collected and subjected to microarray analysis. The data revealed that 365 genes were dysregulated following exposure to chlorpyrifos, cypermethrin and their mixture. Treatment with chlorpyriphos upregulated 194 genes and downregulated 171 genes whereas cypermethrin treatment caused upregulation of 171 genes and downregulation of 152 genes while their combination upregulated 176 genes and downregulated 146 genes (minimum cut off of 12.0 log fold change). Atp5g2, Cox6a1, Tpt1, Hint1, Fau, Rps27, Fth1, Rplp0 Sftpd and Sftpa were among the top ten dysregulated genes in all the treatments groups. Protein-protein interaction analysis showed that Atp5g2, Cox6a1, Tpt1, Hint1, Fau, Rps27, Fth1 and Rplp0 forms a network with each other whereas Sftpd and Sftpa1 are co- expressed. Data taken together suggest that exposure to chlorpyrifos and/or cypermethrin may induce lung damage via dysregulating the expression of Atp5g2, Cox6a1, Tpt1, Hint1, Fau, Rps27, Fth1, Rplp0, Sftpd and Sftpa.. The findings of current study have significance as farm workers get frequent exposures to the cocktail of these pesticides in field situations.

Differential gene expression profile of mice lung following chronic dietary exposure to chlorpyrifos and/or cypermethrin