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Chlorpyrifos-oxon interferes with differentiation of N2a neuroblastoma cells.

E Nikolaidis1, J Flaskos2, M Sachana2*, W Harris3 and A J. Hargreaves3
  • 1 Aristotle University of Thessaloniki, Laboratory of Pharmacology, Greece
  • 2 Aristotle University of Thessaloniki, Laboratory of Biochemistry and Toxicology, Greece
  • 3 Nottingham Trent University, Interdisciplinary Biomedical Research Centre, United Kingdom

Introduction. A rapidly growing body of data over the last decade indicates that two of the organophosphate (OP) ester pesticides, chlorpyrifos (CPF) and diazinon (DZN), are capable of inducing developmental neurotoxicity (DNT) (1). Our previous research shows that both DZN (2) and its main in vivo metabolite, diazinon-oxon (DZO) (3), inhibit neurite outgrowth, a well established in vitro biomarker of DNT (4) in N2a cells. Furthermore, we have shown that CPF also impairs neurite outgrowth in the same cellular model (5, 6).
The aims of the present study were to assess the ability of the oxon in vivo metabolite of CPF, chlorpyrifos-oxon (CPO) to interfere with neurite outgrowth and to investigate the biochemical nature of any morphological effects.
Methods. After 24 h exposure and induction of differentiation, N2a cells were either stained for morphological analysis or processed for SDS-PAGE and Western blotting. The blots were probed with monoclonal antibodies recognizing tubulin (B512) and GAP-43 (GAP-7B10).
Results. Compared to the control, CPO, at a concentration of 10 μM, inhibited the outgrowth of neurites within 24 h. Immunoblot analysis revealed a significant decrease in reactivity with the anti-GAP-43 antibody in N2a cells treated with CPO, whereas there was no change in reactivity with the anti-α-tubulin antibody.
Discussion. The results indicate that CPO causes a significant reduction in the number of neurites similarly to its parent compound (5, 6). In addition, exposure of N2a cells to CPO decreases the levels of GAP-43, an important protein in the maintenance of axons that is known to be increased during axon development. In contrast, the levels of α-tubulin are unaffected by CPO, since tubulin synthesis shows small or no specific increase during axon growth. It is inferred that the DNT which CPF causes in vivo may be partly attributed to its oxon metabolite.

References

1. Flaskos and Sachana. Developmental neurotoxicity of anticholinesterase pesticides. In Anticholinesterase Pesticides: Metabolism, Neurotoxicity and Epidemiology, Gupta RC, Satoh T (eds). John Wiley and Sons, New Jersey, In press.


2. Flaskos et al. (2007) Toxicol Appl Pharmacol 219: 172-180.

3. Sidiropoulou et al. (2009) Arch Toxicol 83: 373-380.

4. Sachana et al. In vitro biomarkers of developmental neurotoxicity In Reproductive and Developmental Toxicology, Gupta RC (ed). Elsevier, San Diego, In press.

5. Sachana et al. (2001) Toxicology In Vitro 15: 369-372.

6. Sachana et al. (2005) Toxicol Mech Methods 15: 405-410.

Keywords: organophosphate ester pesticides, Neurotoxicity, Neuroblastoma

Conference: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010, Thessaloniki, Greece, 1 Oct - 5 Oct, 2010.

Presentation Type: Oral

Topic: Xenobiotic toxicity

Citation: Nikolaidis E, Flaskos J, Sachana M, Harris W and Hargreaves AJ (2010). Chlorpyrifos-oxon interferes with differentiation of N2a neuroblastoma cells.. Front. Pharmacol. Conference Abstract: 8th Southeast European Congress on Xenobiotic Metabolism and Toxicity - XEMET 2010. doi: 10.3389/conf.fphar.2010.60.00169

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Received: 28 Oct 2010; Published Online: 04 Nov 2010.

* Correspondence: Dr. M Sachana, Aristotle University of Thessaloniki, Laboratory of Biochemistry and Toxicology, Thessaloniki, Greece, msachana@vet.auth.gr