Comparison of the skin tumor-promoting potential of different organic peroxides in SENCAR mice.
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.
Gimenez-Conti
I B
IB
M.D. Anderson Cancer Center, Science Park-Research Division, University of Texas, Smithville 78957, USA.
Binder
R L
RL
Johnston
D
D
Slaga
T J
TJ
D000818:Animals; D001585:Benzoyl Peroxide / Q000633:toxicity; D001593:Benzyl Compounds / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D051379:Mice; D018632:Mice, Inbred SENCAR; D010545:Peroxides / Q000633:toxicity*; D012867:Skin / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced*
D001593:Benzyl Compounds; D002273:Carcinogens; D010545:Peroxides; C111570:di-tert-butyl peroxide; C037517:dicumyl peroxide; D001585:Benzoyl Peroxide