Diminution of mouse epidermal superoxide dismutase and catalase activities by tumor promotors
- Oak Ridge National Lab., TN
The effects of phorbol ester tumor promoters and related compounds on superoxide dismutase (SOD) and catalase were examined. The treatment of adult mouse skin with 2 ..mu..g 12-0-tetradecanoylphorbol-13-acetate (TPA) resulted in a sustained decrease in the basal levels of both SOD and catalase activities in the epidermis. A decline in SOD activity occurred within 2 h after application and the maximum effect was seen at 16-17 h. The decrease in SOD activity was always accompanied by a similar decline in the epidermal catalase activity. The alterations in both enzymes occurred against a high background of enhanced protein synthesis which indicates that the effect of TPA is selective for SOD and catalase. Other tumor promoters such as phorbol 12,13-dibutyrate and the non-phorbol tumor promoter anthraline also lowered the activities of both the enzymes. Mezerein, a resiniferonol derivative with weak promoting activity but a potent stage-II promoter, appeared to be more potent than TPA in lowering the basal levels. These results indicate that damage which favors neoplastic progression would occur in TPA-treated mouse skin due to the accumulation of free radicals resulting from low levels of SOD and catalase activity. In addition, the TPA-caused decrease in the levels of SOD and catalase was not prevented by either retinoic acid, fluocinolone acetonide, tosyl amino-2-phenylethyl chloromethyl ketone, or butylated hydroxytoluene, suggesting that inhibition of tumor promotion by these agents is not mediated through alterations in the levels of enzymatic activities which decrease free radical concentrations.
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 6721095
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Vol. 2:11
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
PEROXIDASES
INHIBITION
PHORBOL ESTERS
BIOLOGICAL EFFECTS
EPIDERMIS
MICE
SUPEROXIDE RADICALS
TUMOR PROMOTERS
ANIMAL TISSUES
ANIMALS
BODY
CARBOXYLIC ACIDS
CARCINOGENS
ENZYMES
EPITHELIUM
ESTERS
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PORPHYRINS
PROMOTERS
RADICALS
RODENTS
SKIN
TISSUES
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)