Comparative toxicity of sulfur mustard and nitrogen mustard on tracheal epithelial cells in primary culture

Toxicology in Vitro : an International Journal Published in Association with BIBRA
J H CalvetF Marano

Abstract

Sulfur mustard (SM) and mechlorethamine (HN2) are two alkylating agents. SM represents a potential chemical warfare agent and HN2 is used in cancer chemotherapy. Based on the similarities of their action, although few comparative studies of their effects have been performed on the same model, many compounds effective against HN2 side-effects have been proposed, unsuccessfully, against SM-induced lesions. We performed this study to compare the toxic effects of these two alkylating agents on rabbit tracheal epithelium in primary culture. Using neutral red uptake, we evidenced that for a time of contact of 24hr, HN2 LC(50) was significantly lower than SM LC(50) (0.034+/-0.009 and 0.132+/-0.023mm, respectively; P<0.001). On the other hand, for exposure at 10(-3)m, the time necessary to decrease the cell viability rate to 50% was shorter with SM than with HN2 (11+/-1min and 54+/-2min, respectively; P<0.0001). These two alkylating agents induced apoptosis which was evidenced by DNA ladder and by 4',6-diamidino-2-phenylindole (DAPI) DAPI staining. The apoptosis rates were time and dose dependent for the two toxics: mild doses induced apoptosis, while higher doses induced necrosis.

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Citations

Oct 5, 2016·Journal of the European Academy of Dermatology and Venereology : JEADV·S N EmadiJ Akhavan-Moghaddam
Aug 29, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Angela Cruz-HernandezJared M Brown

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