Comparison of the skin tumor-promoting potential of different organic peroxides in SENCAR mice.

Abstract

The skin tumor-promoting activities of three organic peroxides were evaluated and compared to the activity of benzoyl peroxide, a well-characterized tumor promoter. Two of the compounds (di-t-butyl peroxide and dicumyl peroxide) were dialkyl peroxides and the other (di-m-chlorobenzoyl peroxide) was a diacyl peroxide. These compounds were selected based on a previous study in which we evaluated their capacity to induce epidermal hyperplasia, ornithine decarboxylase activity, and dark basal keratinocytes, which have been reliable short-term markers of tumor promotion. Dicumyl peroxide was a weak tumor promoter despite its high activity in inducing hyperplasia. Like benzoyl peroxide, di-m-chlorobenzoyl peroxide generally had intermediate activity as an inducer of short-term markers of tumor promotion and was a moderately effective tumor promoter. However, compared to benzoyl peroxide, di-m-chlorobenzoyl peroxide was more toxic to the skin, which may have limited its tumor-promoting activity. The final compound, di-t-butyl peroxide, which was essentially inactive in short-term assays, was also totally inactive in promoting papillomas or carcinomas in initiated skin. Tumor-promoting efficacy generally showed an inverse association with thermal stability for the compounds tested, suggesting that the rate of formation 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 these compounds should be useful for studying mechanisms of organic peroxide-induced tumor promotion.

• Authors: I B Gimenez-Conti, R L Binder, D Johnston, T J Slaga
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 149 Issue 1 Pg. 73-9 (Mar 1998) ISSN: 0041-008X [Print] United States
• PMID: 9512729 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzyl Compounds
• Carcinogens
• Peroxides
• di-tert-butyl peroxide
• dicumyl peroxide
• Benzoyl Peroxide

Topics

• Animals
• Benzoyl Peroxide (toxicity)
• Benzyl Compounds (toxicity)
• Carcinogens (toxicity)
• Female
• Mice
• Mice, Inbred SENCAR
• Peroxides (toxicity)
• Skin (drug effects)
• Skin Neoplasms (chemically induced)