Studies on the mechanisms of action of modifiers of skin carcinogenesis

Conference · Tue Jan 01 04:00:00 EST 1980

OSTI ID:5274640

Slaga, T. J.

Skin tumors can be induced by the sequential application of a subthreshold dose of a carcinogen (initiaton phase), followed by repetitive treatment with a weak or noncarcinogenic tumor promoter. There is a very good dose-response relationship between the induction of the number of papillomas per mouse at early times (10 to 20 weeks) by either tumor initiators and promoters and the final carcinoma incidence after a longer latency (20 to 50 weeks) in SENCAR mice. This system not only can be used to determine the tumor initiating and promoting activities of a compound but if the agent is given repeatedly by itself one can also determine if it is a complete carcinogen, i.e., if it has both tumor initiating and promoting activity. There is a good correlation between the tumor-initiating activities of PAH and their abilities to bind covalently to DNA. In addition, various inhibitors of PAH tumor initiation show a strong correlation with their abilities to inhibit the binding of the PAH to DNA and their anti-tumor initiating activities. There is also a good correlation between the promoting abilities of phorbil esters to promote tumors and their abilities to induce ornithine decarboxylase (ODC), cell proliferation and dark basal keratinocytes. However, when other nonpromoting hyperplastic agents are used only dark cell induction correlates. Certain polyamines and prostaglandins can enhance phorbol ester tumor promotion. Anti-inflammatory steroids, retinoids and protease inhibitors are potent inhibitors of tumor promotion. They inhibit tumor promotion by either inhibiting the 12-0-tetradecanoylphorbol-13-acetate (TPA)induced cell proliferation, ODC and/or dark basal keratinocytes. Certain weak promoters such as mezerein which mimics TPA in many biochemical and morphological effects are potent second step promoters in a two-stage promotion regimen.

• Research Organization: Oak Ridge National Lab., TN (USA)
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5274640
• Report Number(s): CONF-800498-1
• Country of Publication: United States
• Language: English

Related Subjects

560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BIOASSAY
BIOLOGICAL MODELS
BODY
CARCINOGENESIS
CHEMICAL BONDS
DISEASES
DNA
DOCUMENT TYPES
DOSE-RESPONSE RELATIONSHIPS
HYDROCARBONS
INHIBITION
MAMMALS
MICE
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
POLYCYCLIC AROMATIC HYDROCARBONS
REVIEWS
RODENTS
SKIN
SYNERGISM
VERTEBRATES