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Multi drug resistance-1 (MDR1) expression in response to chronic diazinon exposure: an in vitro study on Caco-2 cells

Peiman Habibollahi1, Mohammad Hossein Ghahremani, Ebrahim Azizi

  • 1Department of Radiology, Center for Translational Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA.

Bulletin of Environmental Contamination and Toxicology
|December 4, 2010
PubMed

Insights

Chronic exposure to the pesticide diazinon increased Caco-2 cell resistance and growth. This adaptation involved higher P-glycoprotein (P-gp) expression without altering MDR-1 mRNA levels.

Area of Science:

  • Cell Biology
  • Toxicology
  • Pharmacology

Background:

  • The gastrointestinal tract is a primary site for xenobiotic exposure.
  • Understanding cellular responses to pesticides like diazinon is crucial for assessing health risks.

Purpose of the Study:

  • To investigate the effects of chronic diazinon exposure on Caco-2 intestinal cells.
  • To determine the cellular mechanisms underlying resistance to diazinon.

Main Methods:

  • Caco-2 cells were adapted to increasing concentrations of diazinon over 4.5 months.
  • Cell growth was assessed in the presence of varying diazinon concentrations.
  • P-glycoprotein (P-gp) expression and MDR-1 mRNA levels were analyzed.

Main Results:

  • Resistant Caco-2 cells exhibited significantly enhanced growth compared to parent cells under diazinon exposure.
  • P-glycoprotein expression was significantly upregulated in resistant cells.
  • No significant alteration in MDR-1 mRNA levels was observed in resistant cells.

Conclusions:

  • Chronic diazinon exposure induces resistance in Caco-2 cells, characterized by increased cell growth.
  • Upregulation of P-glycoprotein is a key mechanism in diazinon resistance.
  • The observed resistance occurs independently of changes in MDR-1 mRNA levels.

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