Document Detail

Modeling the developmental neurotoxicity of nicotine in vitro: cell acquisition, growth and viability in PC12 cells.
MedLine Citation:
PMID:  15707677     Owner:  NLM     Status:  MEDLINE    
Although nicotine is a developmental neurotoxicant, it also can exert neuroprotective effects. In the current study, we used PC12 cells to determine the developmental phases in which these disparate actions are expressed and to compare the concentrations required for each. In undifferentiated cells, 1 or 10 microM nicotine had little or no effect on cell number (assessed by measuring DNA) but exerted positive trophic actions, characterized by transient enhancement of cell growth (increased total protein/DNA ratio) and persistent enhancement of cell viability (decreased proportions of cells stained with trypan blue). When differentiation was initiated with nerve growth factor, nicotine elicited a different spectrum of actions, with decreases in cell number, impaired neuritic outgrowth (reduced ratio of membrane/total protein) and weakened viability. In either undifferentiated or differentiating cells, nicotine increased lipid peroxidation (determined as thiobarbituric acid reactive species), providing evidence for oxidative damage. Our results indicate that nicotine exerts positive trophic effects primarily on undifferentiated cells, whereas with differentiation the effects undergo a transition to neurotoxicity. These findings support the view that the neurodevelopmental actions of nicotine depend not only upon the magnitude and duration of the exposure, but most importantly on the developmental stage (e.g., differentiation state) in which exposure occurs.
Yael Abreu-Villaça; Frederic J Seidler; Dan Qiao; Theodore A Slotkin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-01-07
Journal Detail:
Title:  Brain research. Developmental brain research     Volume:  154     ISSN:  0165-3806     ISO Abbreviation:  Brain Res. Dev. Brain Res.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-14     Completed Date:  2005-06-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8908639     Medline TA:  Brain Res Dev Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  239-46     Citation Subset:  IM    
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 3813 DUMC, Durham, NC 27710, USA.
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MeSH Terms
Analysis of Variance
Cell Count / methods
Cell Differentiation / drug effects,  genetics
Cell Proliferation / drug effects*
Cell Survival / drug effects
DNA / metabolism
Dose-Response Relationship, Drug
Drug Interactions
Nerve Growth Factor / pharmacology
Neurotoxins / toxicity*
Nicotine / toxicity*
PC12 Cells
Staining and Labeling / methods
Thiobarbituric Acid Reactive Substances / metabolism
Reg. No./Substance:
0/Neurotoxins; 0/Thiobarbituric Acid Reactive Substances; 54-11-5/Nicotine; 9007-49-2/DNA; 9061-61-4/Nerve Growth Factor

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