Responses of human cervical keratinocytes in vitro to tumour promoters and diethylstilboestrol.
dc.contributor.author | Stanley, M | |
dc.contributor.author | Crowcroft, N | |
dc.contributor.author | Quigley, J | |
dc.contributor.author | Parkinson, Eric K | |
dc.date.accessioned | 2010-12-03T10:42:27Z | |
dc.date.available | 2010-12-03T10:42:27Z | |
dc.date.issued | 1985-07 | |
dc.identifier.citation | Responses of human cervical keratinocytes in vitro to tumour promoters and diethylstilboestrol. 1985, 6 (7):1011-5 Carcinogenesis | en |
dc.identifier.issn | 0143-3334 | |
dc.identifier.pmid | 2410159 | |
dc.identifier.doi | 10.1093/carcin/6.7.1011 | |
dc.identifier.uri | http://hdl.handle.net/10541/117088 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.subject | Cancerous Cell Transformation | en |
dc.subject.mesh | Carcinogens | |
dc.subject.mesh | Cell Division | |
dc.subject.mesh | Cell Transformation, Neoplastic | |
dc.subject.mesh | Cells, Cultured | |
dc.subject.mesh | Cervix Uteri | |
dc.subject.mesh | Clone Cells | |
dc.subject.mesh | Diethylstilbestrol | |
dc.subject.mesh | Diterpenes | |
dc.subject.mesh | Female | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Keratins | |
dc.subject.mesh | Kinetics | |
dc.subject.mesh | Phorbols | |
dc.subject.mesh | Terpenes | |
dc.subject.mesh | Tetradecanoylphorbol Acetate | |
dc.title | Responses of human cervical keratinocytes in vitro to tumour promoters and diethylstilboestrol. | en |
dc.type | Article | en |
dc.contributor.department | Department of Pathology, Tennis Court Road, Cambridge CB2 1QP | en |
dc.identifier.journal | Carcinogenesis | en |
html.description.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. |