Document Detail


Prolonged exposure to the candidate microbicide C31G differentially reduces cellular sensitivity to agent re-exposure.
MedLine Citation:
PMID:  16154719     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Comparative assays of in vitro cytotoxicity using nonoxynol-9 (N-9) and the candidate microbicides C31G and sodium dodecyl sulfate (SDS) demonstrated that these agents, which are, respectively, characterized as nonionic, amphoteric, and anionic surfactants, differed in their concentration-dependent effects on cell viability, especially after prolonged exposure. We hypothesized that differences in cellular sensitivity may have been due, in part, to cellular changes induced by long-term exposure to each agent. To examine this possibility, HeLa cells were exposed to N-9, C31G, or SDS for extended periods of time and subsequently reassessed for sensitivity to each of these agents. Following 10 continuous days of C31G exposure, HeLa cells were less sensitive to a subsequent C31G exposure compared to cells that had not undergone long-term C31G treatment. Interestingly, long-term C31G exposure also changed subsequent sensitivity to N-9 but not SDS. In contrast, prolonged exposure to either N-9 or SDS did not reduce sensitivity to re-exposure. The effect of long-term C31G exposure was both concentration-dependent and transient, as treated cells reverted to pre-exposure sensitivity in a time-dependent manner following the cessation of C31G exposure. Lipid analyses of cells exposed to C31G for extended durations revealed altered phospholipid profiles relative to C31G-naïve cells. Experiments examining the individual components of C31G demonstrated the involvement of the amine oxide moiety in reductions in cellular sensitivity. These studies, which provide new information concerning the cytotoxicity of surfactant microbicides, suggest that cervicovaginal epithelial cells may have greater in vivo tolerance for products containing C31G through unique interactions between C31G and components of the cellular membranes.
Authors:
Bradley J Catalone; Mary Lee Ferguson; Shendra R Miller; Dan Malamud; Tina Kish-Catalone; Nina J Thakkar; Fred C Krebs; Mary K Howett; Brian Wigdahl
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie     Volume:  59     ISSN:  0753-3322     ISO Abbreviation:  Biomed. Pharmacother.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-27     Completed Date:  2006-01-30     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8213295     Medline TA:  Biomed Pharmacother     Country:  France    
Other Details:
Languages:  eng     Pagination:  460-8     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
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MeSH Terms
Descriptor/Qualifier:
Amines / chemistry,  pharmacology
Anti-Infective Agents / chemistry,  pharmacology*
Betaine / analogs & derivatives*,  chemistry,  pharmacology
Cell Membrane / drug effects,  metabolism
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Tolerance*
Fatty Acids, Unsaturated / chemistry,  pharmacology*
Hela Cells
Humans
Membrane Lipids / metabolism
Nonoxynol / pharmacology
Sodium Dodecyl Sulfate / pharmacology
Time Factors
Grant Support
ID/Acronym/Agency:
P01 AI37829/AI/NIAID NIH HHS; U19 HD48958/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Amines; 0/Anti-Infective Agents; 0/Fatty Acids, Unsaturated; 0/Membrane Lipids; 107-43-7/Betaine; 151-21-3/Sodium Dodecyl Sulfate; 26027-38-3/Nonoxynol; 693-33-4/hexadecylbetaine; 86903-77-7/C 31G

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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