[ RadSafe ] Radiation Exposure: Does it Always Cause Cancer?

Sat Aug 5 23:41:02 CDT 2006

 Public release date: 3-Aug-2006

Contact: Scott Merville
sdmervil at mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center 
  Researchers identify gene as protector of DNA, enemy of tumors    Houston -- A single gene plays a pivotal role launching two DNA damage detection and repair pathways in the human genome, suggesting that it functions as a previously unidentified tumor suppressor gene, researchers at The University of Texas M. D. Anderson Cancer Center report in Cancer Cell.
  The advance online publication also reports that the gene - called BRIT1 - is under-expressed in human ovarian, breast and prostate cancer cell lines.
  Defects in BRIT1 seem to be a key pathological alteration in cancer initiation and progression, the authors note, and further understanding of its function may contribute to novel, therapeutic approaches to cancer.
  "Disruption of BRIT1 function abolishes DNA damage responses and leads to genomic instability," said senior author Shiaw-Yih Lin, Ph.D., assistant professor in the Department of Molecular Therapeutics at M. D. Anderson. Genomic instability fuels the initiation, growth and spread of cancer.
  A signaling network of molecular checkpoint pathways protects the human genome by detecting DNA damage, initiating repair and halting division of the damaged cell so that it does not replicate.
  In a series of laboratory experiments, Lin and colleagues show that BRIT1 activates two of these checkpoint pathways. The ATM pathway springs into action in response to damage caused by ionizing radiation. The ATR pathway responds to DNA damage caused by ultraviolet radiation.
  By using small interfering RNA (siRNA) to silence the BRIT1 gene, the scientists shut down both checkpoint pathways in cells exposed to either type of radiation.
  Researchers then used siRNA to silence the gene in normal human mammary epithelial cells (HMEC). The result: Inactivation of the gene caused chromosomal aberrations in 21.2 to 25.6 percent of cells. Control group HMEC had no cells with chromosomal aberrations. In cells with the gene silenced that were then exposed to ionizing radiation, 80 percent of cells had chromosomal aberrations. 
  "We also found that BRIT1 expression is aberrant in several forms of human cancer," Lin said. The team found reduced expression of the gene in 35 of 87 cases of advanced epithelial ovarian cancer. They also found reduced expression in breast and prostate cancer tissue compared with non-cancerous cells. 
  Genetic analysis of breast cancer specimens revealed a truncated, dysfunctional version of the BRIT1 protein in one sample.
  Loss of the DNA damage checkpoint function and the ability to proliferate indefinitely are two cellular changes required for the development of cancer. Lin and colleagues have now tied the gene to both factors. They previously identified BRIT1 as a repressor of hTERT, a protein that when reactivated immortalizes cells, allowing them to multiply indefinitely. 
    ###
  Co-authors with Lin are first author Rekha Rai, Ph.D., Hui Dai, M.D., John P. Lahad, M.S., Jiyong Liang, Ph.D., and Gordon Mills, M.D., Ph.D., all of the Department of Molecular Therapeutics; Asha S. Multani, Ph.D., Department of Cancer Genetics at M.D. Anderson; Funda Meric-Bernstam, M.D., Department of Surgical Oncology, M. D. Anderson; Kaiyi Li, Ph.D., Department of Surgery at Baylor College of Medicine; and Koei Chin, M.D., Ph.D., and Joe Gray, Ph.D., of the Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, Calif.

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"George J. Vargo" <vargo at physicist.net> wrote:  Seen at: http://www.ivanhoe.com/channels/p_printStory.cfm?storyid=14249

George J. Vargo, Ph.D., CHP
Senior Scientist
MJW Corporation, Inc.
http://www.mjwcorp.com
610-925-3377
610-925-5545 (fax)
vargo at physicist.net

Reported August 2, 2006 
Radiation Exposure: Does it Always Cause Cancer?
By Vivian Richardson, Ivanhoe Health Correspondent

ORLANDO, Fla. (Ivanhoe Newswire) -- The survivors of the atomic bomb blasts
in Japan during World War II all developed cancer, right?

No. Many did, and suffered terribly, but the fact that a large number of the
survivors have not yet developed cancer is just one part of the mystery
around radiation exposure and cancer.

"I think there is no doubt that radiation is, in fact, carcinogenic," said
Herman Suit, M.D., Ph.D., Sc.D., a radiation oncologist from Harvard
University, today at the 48th Annual Meeting of The American Association of
Physicists in Medicine in Orlando, Florida.

Scientists following 86,611 survivors of the 1945 atomic bomb blasts found
only 4.7 percent of the 10,127 cancer deaths could be clearly attributed to
radiation exposure, said Dr. Suit. These deaths didn't happen right away --
35 percent of the radiation cancer deaths occurred between 42 years and 52
years after the explosions.

"These cancer deaths keep occurring," said Dr. Suit. This reinforces the
need to very carefully study how cancer patients today are affected by the
radiation used to treat their cancers, especially in light of higher
survival rates and life expectancies of these patients.

One of the most perplexing aspects of this area of study is how big a role
genetics seem to play. Dr. Suit explained many studies show that cancer
occurrence increases with increased cancer exposure. In several mouse
studies, however, the rate at which the cancer risk increased varied widely
between different genetic strains of mice. Also, certain types of cancer
seem to be more likely to be caused by radiation exposure than others. He
reported that data from 14 studies show an increased risk for cancers of the
stomach and pancreas while there was no evident increased risk of bladder or
rectal cancer.

"It appears we have made some inroads, but not enough," said Dr. Suit. What
scientists need to know now is the genetic characteristics of specific
patients and how those genes react when exposed to radiation.

This article was reported by Ivanhoe.com, who offers Medical Alerts by
e-mail every day of the week. To subscribe, go to:
http://www.ivanhoe.com/newsalert/.

SOURCE: Vivian Richardson at the 48th Annual Meeting of The American
Association of Physicists in Medicine in Orlando, Fla., July 30-August 3,
2006
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