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Reactive oxygen in the tumor promotion stage of skin carcinogenesis

  • Free Radicals, Antioxidants, Skin Cancer and Related Diseases Symposium Held at the 78th AOCS Annual Meeting in New Orieans, Louisiana, May 1987
  • Published:
Lipids

Abstract

Exposure of isolated SENCAR mouse epidermal cells to the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) in vitro resulted in the production of oxidant species detected as chemiluminescence. This oxidant response can be inhibited by superoxide dismutase and copper complexes but not catalase or scavengers of hydroxyl radical or singlet oxygen, suggesting that the oxidant is superoxide anion. Inhibitors of various parts of the arachidonate cascade affect the TPA-induced oxidant response in a manner that corresponds to their effects on in vivo tumor promotion experiments. Agents that inhibit lipoxygenase activity, i.e. nordihydroguaiaretic acid, benoxaprofen, but not agents that are cyclooxygenase inhibitors, i.e. indomethacin, are effective in suppressing the oxidant response to TPA. Phospholipase C but not phospholipase A2 or D produced an oxidant response kinetically similar to that elicited by TPA. The inhibitors of TPA-induced oxidants inhibited the phospholipase C response to the same extent, suggsting that TPA and phospholipase C may produce an oxidant species through a common mechanism, via phospholipid turnover-protein kinase C activation. The relevance of oxidant production to the tumor promotion process is suggested by the ability of exogenous xanthine/xanthine oxidase, a superoxide anion-generating system, to induce ornithine decarboxylase, a characteristic of TPA-treated cells. In addition, oxidant production is significantly lower in cells from the TPA-promotion resistant C57BL/6J mouse. These studies provide further support for a role for reactive oxygens in the tumor promotion process.

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Abbreviations

CL:

chemiluminescence

CuDIPS:

copper II (3,4-diisopropylsalicylic acid)2

HA-1004:

N-(2-quanidinoethyl)-5-isoquinoline sulfonamide HCl

H-7:

I-(5-isoquinoline sulfonyl)-2-methyl piperazine dihydrochloride

ODC:

ornithine decarboxylase

SOD:

superoxide dismutase

TPA:

12-0-tetradecanoylphorbol-13-acetate.

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Authors and Affiliations

  1. Science Park-Research Division, University of Texas System Cancer Center, Box 389, 78957, Smithville, TX

    Susan M. Fischer, Gregory S. Cameron, James K. Baldwin, Daniel W. Jasheway & Kelly E. Patrick

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  1. Susan M. Fischer
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  2. Gregory S. Cameron
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  3. James K. Baldwin
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  4. Daniel W. Jasheway
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  5. Kelly E. Patrick
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Fischer, S.M., Cameron, G.S., Baldwin, J.K. et al. Reactive oxygen in the tumor promotion stage of skin carcinogenesis. Lipids 23, 592–597 (1988). https://doi.org/10.1007/BF02535603

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  • DOI: https://doi.org/10.1007/BF02535603

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