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    Responses of human cervical keratinocytes in vitro to tumour promoters and diethylstilboestrol.

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    Authors
    Stanley, M
    Crowcroft, N
    Quigley, J
    Parkinson, Eric K
    Affiliation
    Department of Pathology, Tennis Court Road, Cambridge CB2 1QP
    Issue Date
    1985-07
    
    Metadata
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    Abstract
    We have compared the responses of normal human cervical keratinocytes (HCE) to diethylstilboestrol (DES), and the promoting agents, phorbol-12-myristate-13-acetate (PMA) and mezerein using the loss of cloning efficiency as a measure of terminal differentiation in vitro. Dose-response studies showed that normal HCE are growth inhibited by chronic exposure to DES at concentrations greater than or equal to 2.5 X 10(-5) M, to PMA at concentrations greater than 10(-8) M and mezerein at concentrations greater than 10(-9) M. Compared to acetone controls, promoter or DES-treated cells exhibited a 10- to 12-fold increase in cornified-envelope formation. Normal HCE exhibit a heterogeneous response to PMA in that 85-90% of colony-forming cells lose their colony-forming ability after a 24-h exposure to 10(-6) M PMA. The PMA-resistant subpopulation, PMAR, remains constant and is not reduced even after 96 h chronic exposure to PMA. In contrast, the colony-forming ability of normal HCE is almost totally suppressed after 24 h exposure to 10(-6) M mezerein. After 24 h incubation with 5 X 10(-5) M DES, 20% of normal HCE are capable of colony formation but this resistant fraction is eliminated after 96 h chronic exposure. Cornified-envelope formation was negligible in malignant cervical keratinocytes grown in the presence of DES or promotors and these cells were characterised by a very large PMAR fraction - 85 - 90% of cells retained colony-forming ability after exposure to 10(-6) M PMA for 24 h. Furthermore, 90-100% of malignant cervical keratinocytes retained their colony-forming capacity after exposure to 10(-6) M mezerein. However, colony-forming ability declined steadily in the presence of 5 X 10(-5) M DES and after 96 h only a tiny fraction, 1% of malignant cervical keratinocytes could form colonies on replating. The mechanisms by which DES inhibits growth and induces cornified-envelope formation in HCE would appear to be distinct from those activated by PMA and mezerein.
    Citation
    Responses of human cervical keratinocytes in vitro to tumour promoters and diethylstilboestrol. 1985, 6 (7):1011-5 Carcinogenesis
    Journal
    Carcinogenesis
    URI
    http://hdl.handle.net/10541/117088
    DOI
    10.1093/carcin/6.7.1011
    PubMed ID
    2410159
    Type
    Article
    Language
    en
    ISSN
    0143-3334
    ae974a485f413a2113503eed53cd6c53
    10.1093/carcin/6.7.1011
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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