Murine susceptibility to two-stage skin carcinogenesis is influenced by the agent used for promotion
Several approaches were employed to investigate whether murine stock and strain differences in susceptibility to two-stage skin carcinogenesis are due to differences in the metabolism of the initiating aromatic hydrocarbons, or the consequences of the agents used for promotion. A cell-mediated mutagenesis assay was used to quantitatively compare the abilities of cultured newborn SENCAR, DBA/2, C57BL/6 and BALB/c keratinocytes to metabolize dimethylbenz(a)anthracene (DMBA) to mutagenic and cytotoxic metabolites. At equivalent concentrations of DMBA, throughout a 25-fold range in promutagen concentration, C57BL/6, BALB/c and SENCAR keratinocyte-dependent mutant frequencies were very similar and approximately twice DBA/2 keratinocyte-dependent mutant frequencies. In in vivo tumor studies, C57BL/6 mice were more sensitive than SENCAR mice to complete skin carcinogenesis protocols employing repetitive weekly treatments with DMBA and benzo(a)pyrene (BP). At equivalent concentrations of either DMBA or BP, C57BL/6 mice developed carcinomas sooner, and had a greater number of carcinomas per animal. SENCAR mice were very sensitive to two-stage skin carcinogenesis protocols employing BP and DMBA as initiators and benzoyl peroxide and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoters. C57BL/6 mice were relatively refractory to TPA promotion but sensitive to promotion with benzoyl peroxide. These findings suggest that murine stock and strain-dependent differences in sensitivity to two-stage skin carcinogenesis may not be due to major differences in the metabolism of the initiating hydrocarbons, but are partially the consequences of the agents for promotion. 24 references, 5 figures, 1 table.
- Research Organization:
- Univ. of Tennessee-Oak Ridge Graduate School of Biomedical Sciences
- DOE Contract Number:
- W-7405-ENG-26
- OSTI ID:
- 6133426
- Journal Information:
- Carcinogenesis; (United States), Vol. 5:3
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BENZANTHRACENE
CARCINOGEN SCREENING
BENZOPYRENE
MICE
SENSITIVITY
SKIN
CARCINOMAS
BIOLOGICAL VARIABILITY
CARCINOGENESIS
EXPERIMENTAL DATA
METABOLISM
POLYCYCLIC AROMATIC HYDROCARBONS
TOXICITY
TUMOR PROMOTERS
ANIMALS
AROMATICS
BODY
CONDENSED AROMATICS
DATA
DISEASES
HYDROCARBONS
INFORMATION
MAMMALS
NEOPLASMS
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PROMOTERS
RODENTS
SCREENING
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)