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

Wed Nov 2 18:03:05 CST 2005

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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