Oxidative stress has been suggested to play an integral role in the
cancer process. It may be particularly significant during
tumor progression, where there is likely to be a large amount of
free radicals generated by infiltrating inflammatory cells and dying
tumor cells. In order to test this hypothesis, a variety of
free radical scavengers and
antioxidants were assessed for their ability to inhibit
tumor progression. The murine skin multistage
carcinogenesis model was used to generate
papillomas, which are a population of putative precancerous lesions. Various test agents were applied topically to
papillomas in order to determine if they would decrease the incidence of the malignant lesion,
squamous cell carcinoma. The agents tested included:
reduced glutathione (GSH),
butylated hydroxyanisole,
vitamin E,
copper(II) (3,5-diisopropylsalicylate)2,
sodium benzoate, N-acetyl
cysteine and
disulfiram. Under the conditions of our experiments, only GSH and
disulfiram inhibited
tumor progression to a significant degree. Additional studies indicated that GSH prevented
cancer development in a dose-dependent manner. Another experiment demonstrated that when
papillomas received repeated topical applications of
diethylmaleate, a GSH-depleting agent,
tumor progression was enhanced. Collectively these data suggest that sufficient
glutathione levels may be important in preventing
cancer formation.