Effect of malathion on apoptosis of murine L929 fibroblasts: A possible mechanism for toxicity in low dose exposure

L. Masoud, C. Vijayasarathy, M. Fernandez-Cabezudo, G. Petroianu, A. M. Saleh

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

While acute organophosphorous compound poisoning due to inhibition of acetylcholinesterase is a well-established clinical entity, the existence of chronic poisoning due to exposure to low levels of organophosphorous compounds (below the threshold required for cholinergic clinical symptoms) is a hotly debated issue. In this study, we have evaluated the effects of noncholinergic doses of malathion (0.01-20 μM) on apoptosis of murine L929 fibroblasts. Employing flow cytometric and caspase activation analyses we demonstrate that malathion induces apoptosis in L929 cells in a dose- and time-dependent manner. The initiator caspases (caspase-8 and caspase-9) as well as the effector caspase (caspase-3) were activated by the treatment of L929 cells with malathion. Exposure of L929 cells to malathion in the presence of a general inhibitor of caspase, z-VAD-FMK abolished the apoptotic effect of the compound. In addition, malathion induced an increase in the expression of the pro-apoptotic protein p53. However, the induction of p53 expression was subsequent to activation of the caspase cascades. The present findings suggest, that the cytotoxicity of malathion at noncholinergic doses is mediated through caspase-dependent apoptosis.

Original languageEnglish
Pages (from-to)89-102
Number of pages14
JournalToxicology
Volume185
Issue number1-2
DOIs
Publication statusPublished - Mar 14 2003

Keywords

  • Apoptosis
  • Caspases
  • Malathion
  • Organophosphorus compounds
  • p53

ASJC Scopus subject areas

  • Toxicology

Fingerprint

Dive into the research topics of 'Effect of malathion on apoptosis of murine L929 fibroblasts: A possible mechanism for toxicity in low dose exposure'. Together they form a unique fingerprint.

Cite this