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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 73-79 |
| Number of pages | 7 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 149 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pharmacology
- Toxicology
Cite this
Comparison of the skin tumor-promoting potential of different organic peroxides in SENCAR mice. / Gimenez-Conti, I. B.; Binder, R. L.; Johnston, D.; Slaga, Thomas J.
In: Toxicology and Applied Pharmacology, Vol. 149, No. 1, 03.1998, p. 73-79.Research output: Contribution to journal › Article
}
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, Thomas J
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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UR - http://www.scopus.com/inward/citedby.url?scp=0031881802&partnerID=8YFLogxK
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 -