Comparative toxicity of sulfur mustard and nitrogen mustard on tracheal epithelial cells in primary culture.
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.
Calvet
J H
JH
Centre d'Etudes du Bouchet (Defense Medical Research Center), 91710 Vert Le Petit, France; Departement de Physiologie et INSERM U492, Facultéde Médecine de Créteil 94010 France.
Feuermann
M
M
Llorente
B
B
Loison
F
F
Harf
A
A
Marano
F
F