From: Robert J. Bradbury (bradbury@aeiveos.com)
Date: Thu Aug 29 2002 - 05:10:11 MDT
On Thu, 29 Aug 2002, Damien Broderick wrote:
> < When normal cells' DNA was broken into pieces by radiation, cells quickly
> impounded free telomerase into a compartment called the nucleolus. This
> prevents it attaching ends onto the DNA and allows the correct repair
> mechanisms to mend the gap. >
When I first read this, I thought this was a "good" idea (sequestering
the telomerase), but realizing that telomerase only acts in concert
with its RNA primers to extend the specific repeats found in telomeres
I wonder why this would be useful.
> Oh, oh, oh. What about this:
>
> When tumor cells are damaged by radiation or chemical attack, might the
> breaching of their boundaries allow a gale of telomerase to `infect'
> adjacent cells, and maybe render some neoplastic that had all the
> preliminary malign mutations *except* for a switched-on telomerase gene?
There isn't any real "breaching of their boundaries" that I'm aware of.
(Rafal comments?) Radiation will act to produce an increase in double
strand breaks which tends to trigger apoptosis in human cells. Various
chemical toxins could function to either poison the cell or interfere
with the normal cell division processes. I strongly doubt there is
migration of telomerase enzymes between cells.
> Might this give enough of them breathing-space *until* that needed mutation
> occurs by chance in one of the clones? Hence the disheartening finding that
> often the removal of a tumor is followed by new tumors springing up all
> over the place? I understand that this is currently explained by a
> *suppressive* influence exerted by the primary while it's in situ, but
> maybe...
The suppressive influence of a primary is most likely due to the fact
that it has activated genes to suck up all the local resources (glucose,
iron, zinc, etc.). The growth of a primary presumably depends on its
activation of angiogenesis pathways. The growth of secondaries is
presumably due to the activation of metastasis pathways. Presumably
removing the resource drain the primary represents provides more resources
for the secondaries. One can cure cancer by starving the primaries
and the secondaries, unfortunately this method is not usually good
for the prognosis of the patient.
It seems likely that both the primaries and secondaries would
have trumped the telomerase firewall before scaling the angiogenesis
or metastasis barriers. But this is just M.O. -- your conclusions
may vary and should be based on gene chip analysis of the gene expression
in the cells that are misbehaving.
Robert
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