Association of carcinoma yield with early papilloma development in SENCAR mice
The responsiveness of SENCAR mouse skin to 20 different chemicals with known carcinogenic properties was assessed in initiation/promotion experiments. The purpose of these experiments was to evaluate the extent of false negative responses in mouse skin initiation/promotion protocols and to determine the extent to which early papilloma development can be used to predict the eventual development of malignant tumors. The chemicals were administered as initiators by four different routes: oral, intraperitoneal, subcutaneous, and topical. Following the initiating dose of carcinogen, the animals were subjected to topical applications of 1 ..mu..g 12-O-tetradecanoylphorbol-13-acetate (TPA) 3 times per week for a period of 20 weeks. The yield of papillomas at 24 weeks was selected as a potential predictor of carcinoma yields at 52 weeks following the start of the promotion schedule. Positive responses were observed with only eight of the compounds tested. Papilloma yield at 24 weeks following the start of the promotion schedule was clearly related to the development of carcinomas at 52 weeks. No simple linear relationship existed between papilloma yield and carcinoma development, since the number of malignant tumors per papilloma decreased with increasing papilloma yields. The relationship between papilloma and carcinoma yields appeared to be independent of the carcinogen used. These data indicate that there are some limitations in using mouse skin initiation/promotion experiments as the sole basis for identifying substances with carcinogenic activity. However, the test does perform well within certain classes of compounds. Within the limits of these chemical classes, the use of papilloma yield to predict carcinoma yield appears justified.
- Research Organization:
- Washington State Univ., Pullman
- OSTI ID:
- 7145233
- 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
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560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETATES
AFLATOXIN
AMINES
ANIMALS
ANTIGENS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
BODY
CARBOXYLIC ACID SALTS
CARCINOGENESIS
CARCINOGENS
CARCINOMAS
CONDENSED AROMATICS
DISEASE INCIDENCE
DISEASES
ESTERS
HYDROCARBONS
INJECTION
INTAKE
LEAD COMPOUNDS
MAMMALS
MATERIALS
METHYL METHANESULFONATE
MICE
MUTAGENS
NEOPLASMS
NITROSAMINES
NITROSO COMPOUNDS
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PATHOGENESIS
PHORBOL ESTERS
POLYCYCLIC AROMATIC HYDROCARBONS
PROMOTERS
RODENTS
SKIN
SUBCUTANEOUS INJECTION
SULFONIC ACID ESTERS
TOXIC MATERIALS
TOXINS
TUMOR PROMOTERS
VERTEBRATES