Correlation of initiating potency of skin carcinogens with potency to induce resistance to terminal differentiation in cultured mouse keratinocytes

Journal Article · Wed May 01 00:00:00 EDT 1985 · Cancer Res.; (United States)

OSTI ID:5227531

Kilkenny, A E; Morgan, D; Spangler, E F; Yuspa, S H

The induction by chemical carcinogens of resistance to terminal differentiation in cultured mouse keratinocytes has been proposed to represent a cellular change associated with the initiation phase of skin carcinogenesis. Previous results with this culture model indicated that the number of differentiation-resistant foci was correlated with the dose and known potency for several chemical carcinogens. Assay conditions were optimized to provide quantitative results for screening a variety of carcinogens for their potency as inducers of foci resistant to terminal differentiation. Eight skin initiators of varying potency and from different chemical classes and ultraviolet light were studied for their activity to induce this alteration in cultured epidermal cells from newborn BALB/c mice. There was an excellent positive correlation for the potency of these agents as initiators in vivo and as inducers of altered differentiation in vitro. The induction of resistant foci was independent of the relative cytotoxic effects of each agent except where cytotoxicity was extensive and reduced the number of foci. The results support the hypothesis that initiation of carcinogenesis in skin results in an alteration in the program of epidermal cell differentiation. The results also suggest that the assay is useful for identifying relative potency classes (strong, moderate, weak) of initiating agents.

• Research Organization: National Cancer Institute, Bethesda, MD
• OSTI ID: 5227531
• Journal Information: Cancer Res.; (United States), Vol. 5
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
NEOPLASMS
RADIOINDUCTION
SKIN
XENOBIOTICS
CARCINOGEN SCREENING
BIOLOGICAL MODELS
BIOLOGICAL RADIATION EFFECTS
CALCIUM
CARCINOGENS
CELL CULTURES
CELL DIFFERENTIATION
EPIDERMIS
MICE
TOXICITY
ULTRAVIOLET RADIATION
ALKALINE EARTH METALS
ANIMAL TISSUES
ANIMALS
BIOLOGICAL EFFECTS
BODY
DISEASES
ELECTROMAGNETIC RADIATION
ELEMENTS
EPITHELIUM
MAMMALS
METALS
ORGANS
RADIATION EFFECTS
RADIATIONS
RODENTS
SCREENING
TISSUES
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
560121 - Radiation Effects on Cells- External Source- (-1987)