Publications by authors named "Kristen Louis"

2 Publications

  • Page 1 of 1

Comparative toxicity of mono- and bifunctional alkylating homologues of sulphur mustard in human skin keratinocytes.

Toxicology 2017 05 8;382:36-46. Epub 2017 Mar 8.

Defence Research & Development Canada, Suffield Research Center, Box 4000, Medicine Hat, Alberta, T1A 8K6, Canada.

Sulphur mustard (bis(2-chloroethyl) sulphide; agent H) is a vesicant chemical warfare (CW) agent whose mechanism of action is not known with any certainty and for which there are no effective antidotes. It has a pronounced latent period before signs and symptoms of poisoning appear which it shares with the nitrogen mustards, and that differentiates it from other classes of vesicant agents. Sulphur mustard, the sulphur mustard CW agents Q (1,2-bis(2-chloroethylthio) ethane) and T (1,1 bis(2-chloroethylthioethyl) ether), the H partial hydrolysis product hemi-sulphur mustard (2-chloroethyl 2-hydroxyethyl sulphide; HSM), and the commercially available 2-chloroethyl ethyl sulphide (CEES) were characterized with respect to their toxicity in first passage cultures of proliferating human skin keratinocytes, the target cell of H-induced skin vesication. Agents H and T were equitoxic and half as toxic as agent Q. Hemi-sulphur mustard and CEES were approximately six times and seventeen times, respectively less cytotoxic than H. 2-Chloroethyl ethyl sulphide was only slightly less toxic in confluent cultures compared to actively proliferating cells. In contrast, the toxicity of H, Q, T and HSM significantly decreased as the cultures became confluent, paralleling the decreasing sensitivity of skin keratinocytes to H as they leave the basement membrane of the skin. The toxicity of CEES was maximal by 24h. In contrast, the maximal toxicity of the other four agents occurred at 48h, mirroring the latent period observed for these agents in vivo. The markedly different characteristics of toxicity between CEES and the other four test compounds indicate that it is likely that different mechanisms of action are operative between them. Caution should therefore be taken when interpreting the results of studies utilizing CEES as a simulant for the mechanistic study of H, or in the elucidation of medical countermeasures against this CW agent. It is also notable that the toxicity characteristics of the mono-alkylating HSM mirrors those of H, Q and T, suggesting that the bi-alkylating characteristics of these latter compounds may not play as large a role in their toxic effects as commonly thought.
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May 2017

Photocontrol of ion permeation in lipid vesicles with (bola)amphiphilic spirooxazines.

Org Biomol Chem 2016 Jan;14(1):296-308

Department of Chemistry and Biochemistry, Research and Innovation Centre, University of Regina, 3737 Wascana Parkway, Regina, SK S4S 0A2, Canada.

Three (bola)amphiphilic spirooxazines have been synthesized and their photochromism has been characterized. The large biphotochromic structure of 2 significantly affects its conformational flexibility and the rate constants for thermal ring closure are particularly dependent on the lipid phase state. Two comprehensive ion permeation studies were performed to examine the effect of spirooxazine inclusion and isomerization on membrane permeability. In all cases, the open-ring isomers of these spirooxazines are more disruptive in bilayer membranes than their closed-ring isomers. Further, the rate of ion permeation and net release are highly dependent on the lipid bilayer phase state and the relative position of the photochromic moiety in the bilayer membrane. Moreover, the difference in potassium ion permeability under UV and visible irradiation is more pronounced than previously reported photoresponsive membrane disruptors with reversible photocontrols.
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January 2016