To evaluate the effect of chronic exposure to diazinon in the gastrointestinal tract, Caco-2 cells were made resistant by growing in low concentrations of diazinon (0.02 μM) that was gradually increased to 20 μM within 4.5 months. Resistant cells showed significant higher growth in the presence of 15, 45 and 135 μM of diazinon (96.08, 81.80 and 65.16% of control) compared to parent cells (79.71, 71.76 and 29.50% of control, respectively; p < 0.05). P-glycoprotein (P-gp) expression increased significantly in resistant cells (P-gp to beta-actin ratio 0.586 for parent and 1.255 for resistant cells, respectively; p < 0.05) without any alteration in MDR-1 mRNA level (p > 0.05).
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Price includes VAT (USA)
Tax calculation will be finalised during checkout.
Andrew Clayton C, Pellizzari ED et al (2003) Distributions, associations, and partial aggregate exposure of pesticides and polynuclear aromatic hydrocarbons in the Minnesota Children’s Pesticide Exposure Study (MNCPES). J Expo Anal Environ Epidemiol 13(2):100–111
Bailey HC, Deanovic L et al (2000) Diazinon and chlorpyrifos in urban waterways in northern California, USA. Environ Toxicol Chem 19(1):82–87
Cavret S, Videmann B et al (2005) Diazinon cytotoxicity and transfer in Caco-2 cells: effect of long-term exposure to the pesticide. Environmental Toxicology and Pharmacology 20(2):375–380
Ghahremani MH, Cheng P et al (1999) Distinct roles for Galphai2, Galphai3, and Gbeta gamma in modulation offorskolin- or Gs-mediated cAMP accumulation and calcium mobilization by dopamine D2S receptors. J Biol Chem 274(14):9238–9245
Goto M, Masuda S et al (2003) Decreased expression of P-glycoprotein during differentiation in the human intestinal cell line Caco-2. Biochem Pharmacol 66(1):163–170
Gottesman MM, Pastan I (1993) Biochemistry of multidrug-resistance mediated by the multidrug transporter. Annu Rev Biochem 62:385–427
Ibrahim NA, El-Gamal BA (2003) Effect of diazinon, an organophosphate insecticide, on plasma lipid constituents in experimental animals. J Biochem Mol Biol 36(5):499–504
Krapac IG, Roy WR, Smyth CA, Bamhardt ML (1995) Occurrence and distribution of pesticides in soil at agrichemical facilities in Illinois. J Soil Contam 4:209–226
Lecoeur S, Videmann B et al (2006) Effect of organophosphate pesticide diazinon on expression and activity of intestinal P-glycoprotein. Toxicol Lett 161(3):200–209
McCauley LA, Michaels S et al (2003) Pesticide exposure and self reported home hygiene: practices in agricultural families. Aaohn J 51(3):113–119
Neishabouri EZ, Hassan ZM et al (2004) Evaluation of immunotoxicity induced by diazinon in C57bl/6 mice. Toxicology 196(3):173–179
Sanchez-Pena LC, Reyes BE et al (2004) Organophosphorous pesticide exposure alters sperm chromatin structure in Mexican agricultural workers. Toxicol Appl Pharmacol 196(1):108–113
Simcox NJ, Fenske RA et al (1995) Pesticides in household dust and soil: exposure pathways for children of agricultural families. Environ Health Perspect 103(12):1126–1134
Taipalensuu J, Tavelin S et al (2004) Exploring the quantitative relationship between the level of MDR1 transcript, protein and function using digoxin as a marker of MDR1-dependent drug efflux activity. Eur J Pharm Sci 21(1):69–75
Tanaka K, Hirai M et al (1997) Relationship between expression level of P-glycoprotein and daunorubicin transport in LLC-PK1 cells transfected with human MDR1 gene. Biochem Pharmacol 53(5):741–746
Tanigawara Y, Okamura N et al (1992) Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J Pharmacol Exp Ther 263(2):840–845
Ueda K, Okamura N et al (1992) Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone. J Biol Chem 267(34):24248–24252
Wacher VJ, Wu CY et al (1995) Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol Carcinog 13(3):129–134
World Health Organization (WHO) (1998) Environmental health criteria 198: diazinon. In: World Health Organization (Ed.), International program on chemical safety. United Nations Environmental program, Geneva, pp 1–7
About this article
Cite this article
Habibollahi, P., Ghahremani, M.H., Azizi, E. et al. Multi Drug Resistance-1 (MDR1) Expression in Response to Chronic Diazinon Exposure: An In vitro Study on Caco-2 Cells. Bull Environ Contam Toxicol 86, 105–109 (2011). https://doi.org/10.1007/s00128-010-0158-y
- Multi drug resistance 1