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Differentiation of cultured epithelial cells : response to toxic agents

Rice, Robert H., LaMontagne, Anthony D., Petito, Catherine T. and Rong, Xianhui 1989, Differentiation of cultured epithelial cells : response to toxic agents, Environmental health perspective, vol. 80, pp. 239-246.

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Title Differentiation of cultured epithelial cells : response to toxic agents
Author(s) Rice, Robert H.
LaMontagne, Anthony D.ORCID iD for LaMontagne, Anthony D. orcid.org/0000-0002-5811-5906
Petito, Catherine T.
Rong, Xianhui
Journal name Environmental health perspective
Volume number 80
Start page 239
End page 246
Total pages 7
Publisher National Institute of Environmental Health Sciences
Place of publication Durham, N.C.
Publication date 1989
ISSN 0091-6765
Summary 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. Great differences were evident even among those cells derived from stratified squamous epithelia (epidermal, esophageal, vaginal, forestomach) despite their expression of aryl hydrocarbon hydroxylase activities to similar degrees. 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. Although expressing keratinocyte character (transglutaminase activity and envelope forming ability), the cells thus retain some hormonal character that may be modulated by cAMP-dependent kinase activity. 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.
Language eng
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©1989, National Institute of Environmental Health Sciences
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30065767

Document type: Journal Article
Collections: School of Health and Social Development
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.