An apparent inactivation of initiated cells by the potent inhibitor of two-stage mouse skin tumorigenesis, bis(2-chloroethyl)sulfide.

Sulfur mustard, a potent inhibitor of two-stage skin tumorigenesis, appears to act primarily by inactivating initiated cells rather than by suppressing the biochemical response to the promoter ^-O-tetradecanoylphorboMSacetate (TPA). Thus, when the increase of epidermal-dermal p-tosyl-L-arginine methyl ester esterase activity in TPAtreated mice was compared with the response of mice similarly treated but receiving a pretreatment with sulfur mustard, no statistical difference was found. In both cases activity was increased to 4 to 5 times the level found in acetone-treated controls. Moreover, pretreatment with sul fur mustard failed to influence the ability of the promoter to inhibit an isoproterenol-induced accumulation of cyclic adenosine 3':5'-phosphate. Finally, sulfur mustard applied