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- The following strategy
has been adopted in order to investigate a potential chemopreventive
agent at the cellular level. First the ability of the agent to induce growth arrest and apoptosis is
investigated in a panel of cells derived from the target tissue, which
should ideally include one or more cell lines which are as close as
possible to normal tissue, in addition to tumour-derived lines.
Fluorescence activated cell sorting (FACS analysis) is used to
determine the precise effect on cell cycle and to quantitate the level
of apoptosis. A significant difference in sensitivity between tumour
and non-malignant lines is considered beneficial.
- The
ability of the agent to inhibit key signalling pathways involved in
cell proliferation, oncogenic transformation and survival is then
examined.
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- Fig.
legend:
- Mechanisms
of tumour suppression by interference with cellular signalling.
- Red arrows indicate points at which suspected cancer chemopreventive
- agents are known to interfere with growth signals in preneoplastic
cells.
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