Multistage chemical carcinogenesis in mouse skin

Conference · Mon Jan 01 04:00:00 EST 1979

OSTI ID:5907673

Slaga, T J; Fischer, S M; Weeks, C E; Klein-Szanto, A J.P.

Skin tumors in mice can be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a noncarcinogenic tumor promoter. The initiation phase requires only a single application of either a direct acting carcinogen or a procarcinogen which has to be metabolized before being active and is essentially an irreversible step which probably involves a somatic cell mutation. There is a good correlation between the skin tumor initiating activites of several polycyclic aromatic hydrocarbons (PAH) and their ability to bind covalently to epidermal DNA. Laboratory results suggest that bay region diol-epoxides are the ultimate carcinogenic form of PAH carcinogens. Potent inhibitors and stimulators of PAH tumor initiation appear to affect the level of the PAH diol-epoxide reacting with specific DNA bases. Reecent data suggests that the tumor promotion stage involves at least three important steps: (1) the induction of embryonic looking cells (dark cells) in adult epidermis; (2) an increased production of epidermal prostaglandins and polyamines; (3) sustained proliferation of dark cells. Retinoic acid specifically inhibits step two whereas the anti-inflammatory steriod fluocinolone acetonide is a potent inhibitor of steps one and three. The mechanism and the importance of a specific sequence for each step in chemical carcinogenesis in mouse skin are detailed.

• Research Organization: Oak Ridge National Lab., TN (USA)
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5907673
• Report Number(s): CONF-790746-1
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
AROMATICS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MODELS
CARCINOGENESIS
HYDROCARBONS
INHIBITION
KINETICS
ORGANIC COMPOUNDS
PATHOGENESIS
POLYCYCLIC AROMATIC HYDROCARBONS
REACTION KINETICS
STIMULATION
TOXICITY
TUMOR CELLS