Role of cutaneous GSH in 12-O-tetradecanoyl-phorbol 13-acetate-induced mouse skin tumor promotion.

The role of glutathione (GSH) in skin tumor promotion was ascertained in the present study by investigating the effect of the GSH depletor, diethyl-maleate (DEM), on the tumor-promoting ability of TPA in DMBA-initiated mouse skin. DEM lowered the tumor yield and the tumor incidence by 80% (p less than 0.001) in the DMBA + TPA treated group. The rate of tumor formation was also found to be influenced by DEM. The results suggest that clonal expansion of tumor-initiated cells, stimulated by TPA, depends upon the availability of reduced GSH in the tissue. The mechanism by which depletion of reduced GSH could result in inhibition of skin tumor promotion is not known. However, inactivation of GSH and thus blockage of the physiological function of reduced GSH in the biochemical events obligatory to tumor-cell proliferation in mouse skin could be the possible mechanisms providing effective control over proliferation of tumor cells.