TY - JOUR
T1 - Prolonged exposure to the candidate microbicide C31G differentially reduces cellular sensitivity to agent re-exposure
AU - Catalone, Bradley J.
AU - Ferguson, Mary Lee
AU - Miller, Shendra R.
AU - Malamud, Dan
AU - Kish-Catalone, Tina
AU - Thakkar, Nina J.
AU - Krebs, Fred C.
AU - Howett, Mary K.
AU - Wigdahl, Brian
N1 - Funding Information:
We would like to acknowledge the technical assistance of C. Stiller and E. Romaro. In addition, we would like to thank John Moore of Avanti Polar Lipids, Inc. for phospholipid analyses of C31G-treated HeLa cells. These studies were supported by Public Health Service grants P01 AI37829 (M.K. Howett, Program Director; B. Wigdahl, Project 3C Director) and U19 HD48958 (M. Labib, Principal Investigator and B. Wigdahl, Co-Principal Investigator; M. Labib, Project I Director; F. Krebs, Project II Director; B. Wigdahl, Project III Director).
PY - 2005/9
Y1 - 2005/9
N2 - 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.
AB - 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.
KW - C31G
KW - Cytotoxicity
KW - Microbicide
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U2 - 10.1016/j.biopha.2005.07.009
DO - 10.1016/j.biopha.2005.07.009
M3 - Article
C2 - 16154719
AN - SCOPUS:25644448247
SN - 0753-3322
VL - 59
SP - 460
EP - 468
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
IS - 8
ER -