TY - JOUR
T1 - Comparison of the skin tumor-promoting potential of different organic peroxides in SENCAR mice
AU - Gimenez-Conti, I. B.
AU - Binder, R. L.
AU - Johnston, D.
AU - Slaga, T. J.
N1 - Funding Information:
From the Procter & Gamble Company we acknowledge J. E. Thompson and H. L. Vaugh for the synthesis of di-m-chloro-BPO and R. Dykstra for input and discussion on peroxide chemistry. From the University of Texas M. D. Anderson Cancer Center, we acknowledge Lisa Crawford for technical assistance and the Histology Laboratory and the Art Department at the Science Park-Research Division. Special thanks to Carrie McKinley for her secretarial work and help during the preparation of this manuscript. This work was supported by The Procter & Gamble Company.
PY - 1998/3
Y1 - 1998/3
N2 - 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.
AB - 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.
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U2 - 10.1006/taap.1997.8355
DO - 10.1006/taap.1997.8355
M3 - Article
C2 - 9512729
AN - SCOPUS:0031881802
VL - 149
SP - 73
EP - 79
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 1
ER -