[ RadSafe ] Where Broken DNA is Repaired

[Dan W McCarn]

Hi Roy:

Fascinating subject! There was a letter in Nature last October 18, 2006
about Glioma stem cell radiation resistance.  Duke University and MD
Anderson did a study looking at the mechanisms of radiation resistance in
Glioblastoma patients.  They found that a protein present in some of the
Glioma was present which seemed to control the radiation resistance.

The researchers developed a vaccine and were able to suppress some of the
radiation resistance.  I'm not sure if they blocked the CD-133 protein or
the DNA damage checkpoint.  My roommate at Shell Oil benefited from this
research when he was diagnosed in late October with Glioblastoma which
expressed the CD-133 characteristic.  I just happened to read the paper the
week before he fell ill.

Below is the abstract and exact reference for you!

Dan ii

Dan W McCarn, Geologist
Albuquerque & Houston
-------------------------------------------------------------------------
doi:10.1038/nature05236

Glioma stem cells promote radioresistance by preferential activation of the
DNA damage response; Shideng Bao1,2, Qiulian Wu1,2, Roger E. McLendon2,3,
Yueling Hao1,2, Qing Shi1,2, Anita B. Hjelmeland1,2, Mark W. Dewhirst4,
Darell D. Bigner2,3 & Jeremy N. Rich1,2,5,6

Ionizing radiation represents the most effective therapy for glioblastoma
(World Health Organization grade IV glioma), one of the most lethal human
malignancies1, but radiotherapy remains only palliative2 because of
radioresistance. The mechanisms underlying tumour radioresistance have
remained elusive. Here we show that cancer stem cells contribute to glioma
radioresistance through preferential activation of the DNA damage checkpoint
response and an increase in DNA repair capacity. The fraction of tumour
cells expressing CD133 (Prominin-1), a marker for both neural stem cells and
brain cancer stem cells3-6, is enriched after radiation in gliomas. In both
cell culture and the brains of immunocompromised mice, CD133-expressing
glioma cells survive ionizing radiation in increased proportions relative to
most tumour cells, which lack CD133. CD133-expressing tumour cells isolated
from both human glioma xenografts and primary patient glioblastoma specimens
preferentially activate the DNA damage checkpoint in response to radiation,
and repair radiation-induced DNA damage more effectively than CD133-negative
tumour cells. In addition, the radioresistance of CD133-positive glioma stem
cells can be reversed with a specific inhibitor of the Chk1 and Chk2
checkpoint kinases. Our results suggest that CD133-positive tumour cells
represent the cellular population that confers glioma radioresistance and
could be the source of tumour recurrence after radiation. Targeting DNA
damage checkpoint response in cancer stem cells may overcome this
radioresistance and provide a therapeutic model for malignant brain cancers.

1Department of Surgery, 2Preston Robert Tisch Brain Tumor Center, Department
of Pathology, 4Department of Radiation Oncology, 5Department of Medicine,
and 6Department of Neurobiology, Duke University Medical Center, Durham,
North Carolina 27710, USA.

-----Original Message-----
From: radsafe-bounces at radlab.nl [mailto:radsafe-bounces at radlab.nl] On Behalf
Of ROY HERREN
Sent: Thursday, August 02, 2007 23:08
To: radsafe at radlab.nl
Subject: [ RadSafe ] Where Broken DNA is Repaired

http://www.lbl.gov/Science-Articles/Archive/LSD-broken-DNA.html
   
  Where Broken DNA is Repaired  BERKELEY, CA - Ionizing radiation, toxic
chemicals, and other agents continually damage the body's DNA, threatening
life and health: unrepaired DNA can lead to mutations, which in turn can
lead to diseases like cancer. Intricate DNA repair mechanisms in the cells'
nuclei are constantly working to fix what's broken, but whether the repair
work happens "on the road" - right where the damage occurs - or "in the
shop" - at specific regions of the nucleus - is an unanswered question. 
   
  Click on the hyper-text at the top of this page for the full article


Roy Herren
       
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