Phorbol myristate acetate and catechol as skin cocarcinogens in SENCAR mice
The enhancement of the carcinogenicity of benzo(a) pyrene (B(a)P) and ..beta..-propiolactone (BPL) by the mouse skin cocarcinogens phorbol myristate acetate (PMA) and catechol were examined in female SENCAR mice, 30 per group. The carcinogen and cocarcinogen were applied simultaneously, three times weekly for 490-560 days. B(a)P and BPL were used at constant doses of 5 and 50 ..mu..g, respectively, in all experiments. PMA was used at three doses, 2.5, 1.0, and 0.5 ..mu..g per application, and catechol was used at one dose, 2 mg per application. Control groups included animals that received carcinogen only, cocarcinogen only, acetone only, and no treatment. The carcinogenicity of B(a)P and BPL were enhanced by the cocarcinogens, particularly in terms of tumor multiplicity. For both carcinogens, the most marked cocarcinogenic effects were observed at the lowest dose of PMA used (0.5 ..mu..g per application). This observation applied for days to first tumor, animals with tumors, tumor multiplicity, and incidence of malignant skin tumors. Catechol applied alone did not induce any tumors; with PMA alone there were significant incidences of benign and malignant tumors, e.g., at a dose of only 0.5 ..mu..g per application, 15 of 30 animals had 28 tumors, 5 of which were squamous carcinomas. In two-stage carcinogenesis experiments with 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and PMA as promoter, SENCAR mice showed a greater susceptibility to tumor induction when compared to ICR/Ha mice used in earlier work. This susceptibility was most notable in terms of rate of tumor appearance and tumor multiplicity.
- Research Organization:
- New York Univ. Medical Center, NY
- OSTI ID:
- 6966172
- Journal Information:
- Environ. Health Perspect.; (United States), Vol. 68
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BENZOPYRENE
BIOLOGICAL EFFECTS
CARCINOGENESIS
BIOLOGICAL MODELS
CATECHOLAMINES
TETRADECANOIC ACID
MICE
PHORBOL ESTERS
SKIN
TUMOR PROMOTERS
AMINES
ANIMALS
AROMATICS
BODY
CARBOXYLIC ACIDS
CARCINOGENS
CONDENSED AROMATICS
ESTERS
HYDROCARBONS
HYDROXY COMPOUNDS
MAMMALS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHENOLS
POLYPHENOLS
PROMOTERS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology