[ RadSafe ] RE: [Know_Nukes] Article: RADIATION AND THE MICROENVIRONMENT TUMORIGENESIS AND THERAPY

Thu Nov 3 09:40:24 CST 2005

Jim,
Thanks for posting the link.  I am hesitant as
sometimes they do not work, or people do not want to
register.  

Again, biology is not like physics.  We have a lot of
learn.  For example,
". . . The irradiation of cells in vivo results in
fewer cells with chromosomal defects, and far fewer
chromosome abnormalities per cell, compared with in
vitro-derived irradiated cells. One possible
explanation for the difference might be the presence
of in vivo tissue-defense mechanisms that recognize
and remove aberrant cells. Apoptosis is generally
regarded as a non-inflammatory process42, 43 and so
would reduce the number of damaged cells in vivo.
However, in some circumstances, such as the acute
injury response that occurs following IR, the
resulting enzymatic activity associated with
phagocytosis of damaged cells can increase the release
of inflammatory cytokines as well as DNA-damaging free
radicals44-46. Wright and colleagues have postulated
that the delayed appearance of genomically unstable
haematopoietic cells in irradiated mice is consistent
with a long-lived tissue reaction to injury by
irradiation that is characteristic of an inflammatory
response acting in a 'bystander' fashion25."

--- "Muckerheide, James" <jimm at wpi.edu> wrote:

> Thanks John.
> 
> Friends, note that Nature is currently billing as a
> "Free access - Special
> Feature" article (with free registration).  You can
> try:
>
http://www.nature.com/nrc/journal/v5/n11/full/nrc1735_fs.html
>  
> 
> Mary Helen's work in recent years reflects the fact
> that DNA damage is
> largely irrelevant to radiation effects in the light
> of the general
> biological stimulation and repair mechanisms that
> govern responses, while DNA
> damage itself is much greater from normal metabolism
> than from even
> relatively high-dose radiation.  She started from
> concerns about breast
> cancer and radiation therapy, to focus on responses
> in tissues rather than
> cells.
> 
> Regards, Jim Muckerheide
> ========================
> 
> 
> > -----Original Message-----
> > From: Know_Nukes at yahoogroups.com
> [mailto:Know_Nukes at yahoogroups.com] On
> > Behalf Of John Jacobus
> > Sent: Wednesday, November 02, 2005 5:40 PM
> > To: radsafe; know_nukes at yahoogroups.com
> > Subject: [Know_Nukes] Article: RADIATION AND THE
> MICROENVIRONMENT
> > TUMORIGENESIS AND THERAPY
> > 
> > This appeared in Nature Reviews Cancer 5, 867-875
> > (2005)
> > 
> > It is a long article [1081K], so I have only
> supplied
> > the first few paragraphs.  If you would like to
> see
> > the whole article, let me know, as this is an
> > education opportunity.
> > 
> > Mary Helen Barcellos-Hoff1, Catherine Park2 & Eric
> G.
> > Wright3   about the authors
> > 
> > 1 Life Sciences Division, Lawrence Berkeley
> National
> > Laboratory, 1 Cyclotron Road, Berkeley, California
> > 94720, USA.
> > 2 Department of Radiation Oncology, University of
> > California, San Francisco, San Francisco,
> California
> > 94143, USA.
> > 3 Department of Molecular and Cellular Pathology,
> > University of Dundee, Ninewells Hospital and
> Medical
> > School, Dundee DD19SY, Scotland, UK.
> > 
> > correspondence to: Mary Helen Barcellos-Hoff
> > mhbarcellos-hoff at lbl.gov
> > 
> > Radiation rapidly and persistently alters the
> soluble
> > and insoluble components of the tissue
> > microenvironment. This affects the cell phenotype,
> > tissue composition and the physical interactions
> and
> > signalling between cells. These alterations in the
> > microenvironment can contribute to carcinogenesis
> and
> > alter the tissue response to anticancer therapy.
> > Examples of these responses and their implications
> are
> > discussed with a view to therapeutic intervention.
> > 
> > IONIZING RADIATION (IR) is both a carcinogen and a
> > therapeutic agent - low-dose exposure can increase
> an
> > individual's risk of developing cancer, but when
> given
> > at high doses it can slow or stop tumour growth
> (Box
> > 1). How can IR have such a broad range of effects?
> > Studies into the cellular effects of IR have led
> > scientists to a detailed understanding of the cell
> > cycle, DNA damage, apoptosis and the molecular
> > machines that initiate and execute DNA repair.
> Cancer
> > radiotherapy relies on two essential components -
> > killing cancer cells while sparing normal tissues.
> > This is achieved in part by taking advantage of
> the
> > physical attributes of IR that, through
> sophisticated
> > planning and delivery techniques, make it possible
> to
> > safely increase the radiation dose to the tumour
> while
> > limiting the dose to surrounding normal tissues95.
> > Further therapeutic benefits can be accrued by
> > understanding and manipulating the biological
> response
> > of the microenvironment to IR to increase a
> tumour's
> > sensitivity to radiation or to inhibit deleterious
> > effects, respectively.
> > 
> > Many people assume that one must look no further
> than
> > IR-induced DNA damage to understand how it
> functions
> > as a carcinogen and can be used to kill cancer
> cells.
> > However, IR has many multicellular effects,
> indicating
> > that additional mechanisms might contribute to the
> > response to and consequences of IR exposure. In an
> > intact organism, all cells are subject to complex
> > regulatory mechanisms that depend on their
> > interactions with the cells and cellular products
> that
> > comprise their microenvironment. Therefore, the
> > effects of an agent such as IR should not just be
> > considered in terms of isolated cells, but rather
> that
> > the entire tissue has a role in determining the
> > response of any individual cell to any regulatory
> or
> > damaging signals.
> > 
> > When cells are exposed to IR, DNA damage induces a
> > stress response through activation or repression
> of
> > distinct target proteins that primarily function
> to
> > facilitate DNA repair and prevent the
> proliferation of
> > damaged cells. Similar to the stress response
> > programme within cells, IR induces multicellular
> > programmes that orchestrate a response to damage
> at
> > the tissue level1. Such programmes are executed by
> > soluble signals such as CYTOKINES, GROWTH FACTORS
> AND
> > CHEMOKINES, which function on the PARENCHYMA and
> > STROMA to modulate cell behaviours and phenotypes.
> IR
> > can elicit an 'activated' phenotype in some cells
> that
> > promotes rapid, persistent stromal remodelling of
> the
> > EXTRACELLULAR MATRIX (ECM). Remodelling of the ECM
> > occurs through the induction of proteases and
> growth
> > factors, and the chronic production of REACTIVE
> OXYGEN
> > SPECIES (ROS). Tissue responses to IR seem to be
> > directed towards limiting damage, inducing repair
> and
> > restoring tissue homeostasis. However, as with
> most
> > tissue processes, this response can be disrupted
> by
> > high doses of radiation, pre-existing conditions
> such
> > as previous exposure, and the genetic features of
> the
> > individual (Fig. 1).
> > 
> > . . .
> > 
> > +++++++++++++++++++
> > On Oct. 5, 1947, in the first televised White
> House address, President
> > Truman asked Americans to refrain from eating meat
> on Tuesdays and poultry
> > on Thursdays to help stockpile grain for starving
> people in Europe.
> > 
> > -- John
> > John Jacobus, MS
> > Certified Health Physicist
> > e-mail:  crispy_bird at yahoo.com
> > 
> > 
> > 
> > __________________________________
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> > 
> > 
> > http://groups.yahoo.com/group/Know_Nukes
> > 
> 
=== message truncated ===

+++++++++++++++++++
On Oct. 5, 1947, in the first televised White House address, President Truman asked Americans to refrain from eating meat on Tuesdays and poultry on Thursdays to help stockpile grain for starving people in Europe. 

-- John
John Jacobus, MS
Certified Health Physicist
e-mail:  crispy_bird at yahoo.com

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