Document Detail


Sub-lethal genotoxicity and cell alterations by organophosphorus pesticides in MCF-7 cells: Implications for environmentally-relevant concentrations.
MedLine Citation:
PMID:  21137095     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Organophosphorus pesticide (OPP) toxicity is believed to be mediated through inhibition of acetylcholinesterase (AChE). Given their widespread distribution in aquatic systems and their ability to undergo chemical transformation, their environmental impacts at sublethal concentrations in non-target organisms have become an important question. We conducted a number of mammalian-cell genotoxic and gene expression assays, and examined cellular biochemical changes following low-dose exposure of MCF-7 cells to fenitrothion, diazinon and the aqueous degradate of diazinon, 2-isopropyl-6-methyl-4-pyrimidinol (IMP). Following exposure to the OPPs at low concentrations (10(-12) M to 10(-8) M), >2-fold elevations in micronucleus formation were noted in MCF-7 cell cultures that went on to exhibit >75% clonogenic survival; these levels of chromosomal damage were comparable to those induced by 10(-6) M benzo[α]pyrene, a known genotoxic agent. At this low concentration range, a fenitrothion-induced 2-fold elevation in B-cell leukaemia/lymphoma-2 (BCL-2) and cytochrome P450 isoenzyme (CYP1A1) gene expressions was observed. Principal component analysis-linear discriminant analysis (PCA-LDA) of derived infrared (IR) spectra of vehicle control (non-exposed) and OPP-exposed cells highlighted that both fenitrothion and diazinon induced marked biochemical alterations in the lipid, protein and DNA/RNA absorbance regions. Our findings demonstrate that the two OPP parent chemicals and IMP degradate can mediate a number of toxic effects or cellular alterations at very low concentrations. These are independent of just selective inhibition of AChE, with potential consequences for non-target organisms exposed at environmentally-relevant concentrations. Further assays on relevant aquatic organism cell-lines are now recommended to understand the mechanistic low-dose toxicity of these chemicals present in aquatic systems. © 2010 SETAC.
Authors:
Justina Ukpebor; Valon Llabjani; Francis L Martin; Crispin Halsall
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2010-12-6
Journal Detail:
Title:  Environmental toxicology and chemistry / SETAC     Volume:  -     ISSN:  1552-8618     ISO Abbreviation:  -     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8308958     Medline TA:  Environ Toxicol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Lancaster Environment Centre, Lancaster University, Lancaster LA1 4YQ, United Kingdom.
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