Differentiation of cultured epithelial cells: Response to toxic agents
- Charles A. Dana Laboratory of Toxicology, Boston, MA (USA)
Cell culture systems are instrumental in elucidating regulation of normal function and mechanisms of its perturbation by toxic substances. To this end, three applications of epithelial cells cultured with 3T3 feeder layer support are described. First, treatment of the premalignant human epidermal keratinocyte line SCC-12F2 with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate suppressed cell growth and differentiation. This agent produced a biphasic growth response greatly inhibiting cell growth at 1 to 10 nM, but much less above 100 nM. Expression of the differentiated functions involucrin and transglutaminase was found to be inhibited markedly at concentrations above 10 nM. Second, 3-methylcholanthrene toxicity was surveyed in a variety of rat epithelial cell types. The two most sensitive to growth inhibition were epidermal and mammary epithelial cells, while those from bladder, prostate, thyroid, and endometrium were insensitive to growth inhibition. Finally, expression of estrogen receptors in rat endometrial cells was shown to be stimulated by the cAmP-elevating agent forskolin. Maximal stimulation of 3- to 6-fold occurred in 6 hr, compatible with a requirement for protein synthesis. Pursuit of such results will aid in understanding differences in response among cell types and species, in elucidating mechanisms of action of known toxic substances and, ultimately, in predicting toxicity of less well understood agents.
- OSTI ID:
- 5668264
- Journal Information:
- Environmental Health Perspectives; (USA), Vol. 80; ISSN 0091-6765
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
EPITHELIUM
CELL DIFFERENTIATION
PHORBOL ESTERS
BIOLOGICAL EFFECTS
POLYCYCLIC AROMATIC HYDROCARBONS
3-METHYLCHOLANTHRENE
BIOCHEMICAL REACTION KINETICS
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ESTROGENS
PUTRESCINE
RECEPTORS
SKIN
TRITIUM COMPOUNDS
AMINES
ANIMAL TISSUES
AROMATICS
BODY
CARCINOGENS
ESTERS
HORMONES
HYDROCARBONS
HYDROGEN COMPOUNDS
KINETICS
MEMBRANE PROTEINS
ORGANIC COMPOUNDS
ORGANS
PROTEINS
REACTION KINETICS
STEROID HORMONES
TISSUES
560300* - Chemicals Metabolism & Toxicology