Phorbol myristate acetate and catechol as skin cocarcinogens in SENCAR mice

Journal Article · Mon Sep 01 04:00:00 EDT 1986 · Environ. Health Perspect.; (United States)

DOI:https://doi.org/10.1289/ehp.866833· OSTI ID:6966172

Van Duuren, B L; Melchionne, S; Seidman, I

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), Journal Name: Environ. Health Perspect.; (United States) Vol. 68; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
BODY
CARBOXYLIC ACIDS
CARCINOGENESIS
CARCINOGENS
CATECHOLAMINES
CONDENSED AROMATICS
ESTERS
HYDROCARBONS
HYDROXY COMPOUNDS
MAMMALS
MICE
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PHENOLS
PHORBOL ESTERS
POLYPHENOLS
PROMOTERS
RODENTS
SKIN
TETRADECANOIC ACID
TUMOR PROMOTERS
VERTEBRATES