COMPARISON OF THE SKIN TUMOR-PROMOTING POTENTIAL OF DIFFERENT ORGANICPEROXIDES IN SENCAR MICE

The skin tumor-promoting activities of three organic peroxides were ev aluated and compared to the activity of benzoyl peroxide, a well-chara cterized tumor promoter. Two of the compounds (dit-butyl peroxide and dicumyl peroxide) were dialkyl peroxides and the other (di-m-chloroben zoyl peroxide) was a diacyl peroxide. These compounds were selected ba sed on a previous study in which we evaluated their capacity to induce epidermal hyperplasia, ornithine decarboxylase activity, and dark bas al keratinocytes, which have been reliable short-term markers of tumor promotion. Dicumyl peroxide was a weak tumor promoter despite its hig h activity in inducing hyperplasia. Like benzoyl peroxide, di-m-chloro benzoyl peroxide generally had intermediate activity as an inducer of short-term markers of tumor promotion and was a moderately effective t umor promoter. However, compared to benzoyl peroxide, di-m-chlorobenzo yl peroxide was more toxic to the skin, which may have limited its tum or-promoting activity. The final compound, di-t-butyl peroxide, which was essentially inactive in short-term assays, was also totally inacti ve in promoting papillomas or carcinomas in initiated skin. Tumor-prom oting efficacy generally showed an inverse association with thermal st ability for the compounds tested, suggesting that the rate of formatio n of free radicals is a key factor contributing to tumor promotion by organic peroxides. However, a number of other factors can potentially affect the activity of different organic peroxides as tumor promoters. Each compound evaluated had a different spectrum of activities, and t hese compounds should be useful for studying mechanisms of organic per oxide-induced tumor promotion. (C) 1998 Academic Press.