Inhibition of Skin Tumor Initiation, Promotion, and Progression by Antioxidants and Related Compounds

Thomas J. Slaga

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

: Antioxidants have been shown to inhibit the induction of cancer by a wide variety of chemical carcinogens and radiation at many target sites in mice, rats, hamsters, and man. Evidence is accumulating that suggests that free radicals are important in all stages of chemical carcinogenesis. Both carcinogens and tumor promoters have also been shown to decrease the cellular activity of superoxide dismutase and catalase. A number of antioxidants and related compounds were tested to determine if they would inhibit either skin tumor initiation, promotion, or progression. In terms of skin tumor initiation, compounds such as BHT, vitamins E and C, and CuDIPS have been found to inhibit DMBA skin tumor initiation. The mechanism of action of these compounds appears to be related to their effect on the metabolism of DMBA, as BHT and CuDIPS do not inhibit the initiating activity of BP-diol-epoxide and MNNG. Although several antioxidants do inhibit skin tumor initiation by procarcinogens, antioxidants are in general much more effective inhibitors of skin tumor promotion. BHT, BHA, parahydroxyanisole, disulfiran, and vitamins E and C as well as many other antioxidants are very effective inhibitors of skin tumor promotion. We also determined the effect of free radical scavengers on the progression process. Of the agents tested, glutathione and N-acyl dehydroalamines were the most effective in reducing carcinoma incidence. Diethyl maleate, a chemical that reduces glutathione levels, was effective in enhancing progression. In addition, overexpression of ϒ-glutamyltranspeptidasc (GGT), which leads to a reduction in cellular glutathione levels, also enhances progression. These results suggest that GGT has a functional role in skin tumor progression, and that a number of antioxidants are either effective inhibitors of skin tumor initiation, promotion, or progression.

Original languageEnglish (US)
Pages (from-to)51-57
Number of pages7
JournalCritical Reviews in Food Science and Nutrition
Volume35
Issue number1-2
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Keywords

  • SOD
  • antioxidants
  • carcinogenesis
  • catalase
  • free radicals
  • glutathione peroxidase

ASJC Scopus subject areas

  • Food Science
  • Industrial and Manufacturing Engineering

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