Studies on the mechanisms involved in multistage carcinogenesis in mouse skin
Skin tumors can be effectively induced in mice by the repetitive application of a carcinogen. The relative order of sensitivity to complete carcinogenesis is Sencar > CD-1 > C57BL/6 greater than or equal to BALB/c greater than or equal to ICR/Ha Swiss > C3H. Skin tumors in mice can also be induced by the sequential application of a subthreshold dose of a carcinogen (initiation phase) followed by repetitive treatment with a weak or noncarcinogenic tumor promoter (promotion phase) followed by repetitive treatment with a weak or noncarcinogenic tumor promoter (promotion phase). The relative order of sensitivity to initiation-promotion is Sencar > > CD-1 > ICR/Ha Swiss greater than or equal to Balb/c > C57BL/6 greater than or equal to C3H greater than or equal to DBA/2. The phorbol ester tumor promoters have been shown to have several cellular and biochemical effects on the skin. Of all the observed phorbol ester related effects on the skin, the induction of epidermal cell proliferation, polyamines, prostagladins, and dark basal keratinocytes as well as other embryonic conditions appear to correlate the best with promotion. Mezerein, a weak promoter, was found to induce many cellular and biochemical changes similar to 12-O-tetradecanoylphorbol-13 acetate (TPA), especially epidermal hyperplasia and polyamines; however, it was not a potent inducer of dark cells. Although C57BL/6 mice are relatively resistant to initiation-promotion by PAH initiation and phorbol ester promotion, they are fairly sensitive to complete carcinogenesis by PAH. This suggests that the C57BL/6 mice are resistant to phorbol ester tumor promotion. Preliminary experiments suggest that C57BL/6 and Sencar mice respond qualitatively but not quantitatively to a single treatment with TPA.
- Research Organization:
- Oak Ridge National Lab., TN
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 5983530
- Journal Information:
- J. Cell. Biochem.; (United States), Vol. 18
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
CARCINOGENESIS
BIOLOGICAL PATHWAYS
POLYCYCLIC AROMATIC HYDROCARBONS
BIOLOGICAL EFFECTS
CARCINOGENS
COMPARATIVE EVALUATIONS
DNA
MICE
NEOPLASMS
SENSITIVITY
SKIN
TUMOR PROMOTERS
ANIMALS
AROMATICS
BODY
DISEASES
HYDROCARBONS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PROMOTERS
RODENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550200 - Biochemistry