Featured Research

from universities, journals, and other organizations

Drug mitigates toxic effects of radiation in mice

Date:
June 24, 2010
Source:
University of North Carolina School of Medicine
Summary:
Medical researchers have provided one of the first examples of successful radiomitigation in mammals. The investigators found that oral treatment of mice with a drug that inhibits enzymes involved in cell division caused certain groups of bone marrow cells to temporarily stop dividing (which they termed "pharmacological quiescence" or PQ).

While radiation has therapeutic uses, too much radiation is damaging to cells. The most important acute side effect of radiation poisoning is damage to the bone marrow. The bone marrow produces all the normal blood cells, and therefore a high dose of radiation can lead to low blood counts of red cells, platelets and white blood cells. Humans that receive a lethal dose of radiation as in the setting of an accidental exposure die of bone marrow failure. While there are a few drugs that will decrease toxicity when given before exposure to radiation ("radioprotectants"); currently, no effective therapy exists to mitigate bone marrow toxicity of radiation when given after radiation exposure ("radiomitigants"). The identification of successful human radiomitigants is a top research priority of the U.S. Department of Homeland Security and National Institutes of Health.

In a study published June 23 in the Journal of Clinical Investigation, a team led by UNC Lineberger Associate Director for Translational Research, Norman Sharpless, MD, provides a first example of successful radiomitigation in mammals. The investigators found that oral treatment of mice with a drug that inhibits enzymes involved in cell division caused certain groups of bone marrow cells to temporarily stop dividing (which they termed 'pharmacological quiescence' or PQ). Several decades of work have shown that cells which are not dividing are resistant to agents that damage DNA, like radiation. Workers in the Sharpless lab were then able to show that the induction of PQ immediately before or up to 20 hours after radiation exposure were able to protect mice from a lethal dose of radiation. PQ protected all the normal cells of blood, including platelets, red cells and white cells.

"We believe this study is really exciting. We have identified a simple, non-toxic pill that decreases radiation toxicity even when given after radiation exposure. We believe this approach could be of use in humans who are accidentally or intentionally exposed to lethal doses of radiation," said Sharpless, who is an associate professor of medicine and genetics at UNC's School of Medicine.

PQ relies on the use of potent and selective inhibitors of cellular enzymes called CDK4 and CDK6. Related drugs have been used extensively in humans with cancer, and CDK4/6 inhibitors are currently being tested in humans. Importantly, these drugs can be given as a pill, are chemically stable and have little toxicity. Therefore, such compounds could be stockpiled for use in the setting of an unexpected radiological disaster. The group showed that structurally different versions CDK4/6 inhibitors provided protection from radiation, whereas other types of kinase inhibitors did not.

Sharpless believe PQ may have a role in treating patients with cancer. Radiation is used in cancer therapy, and therefore PQ might benefit such patients. Also, several commonly used chemotherapy drugs cause bone marrow toxicity by damaging DNA, and therefore PQ might protect from chemotherapy toxicity in addition to radiation toxicity. A concern is that PQ might also protect a patient's tumor from the toxicity of therapeutic DNA damaging agents, but the Sharpless group showed that at least some types of cancer were not protected by inhibitors of CDK4/6. Bone marrow protection is a major issue in medical oncology, with billions of dollars of growth factors used annually in the US alone for this problem. In particular, PQ protects platelets and red cells, which are largely unmet needs in current clinical oncology.

UNC has filed patents related to these discoveries, which have been licensed to an RTP-startup company called G-Zero Therapeutics, which was co-founded in 2007 by Sharpless and researchers in Boston and San Franscisco.

This work was supported by the University of North Carolina Lineberger Comprehensive Cancer Center Mouse Phase I Unit and grants from the Golfers Against Cancer Foundation, the Ellison Medical Foundation, the Burroughs Wellcome Fund, and the National Institutes of. J.F. Bell was supported by a career development award from the V Foundation for Cancer Research.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sψren M. Johnson, Chad D. Torrice, Jessica F. Bell, Kimberly B. Monahan, Qi Jiang, Yong Wang, Matthew R. Ramsey, Jian Jin, Kwok-Kin Wong, Lishan Su, Daohong Zhou and Norman E. Sharpless. Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. Journal of Clinical Investigtion, June 23, 2010 DOI: 10.1172/JCI41402

Cite This Page:

University of North Carolina School of Medicine. "Drug mitigates toxic effects of radiation in mice." ScienceDaily. ScienceDaily, 24 June 2010. <www.sciencedaily.com/releases/2010/06/100623123357.htm>.
University of North Carolina School of Medicine. (2010, June 24). Drug mitigates toxic effects of radiation in mice. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2010/06/100623123357.htm
University of North Carolina School of Medicine. "Drug mitigates toxic effects of radiation in mice." ScienceDaily. www.sciencedaily.com/releases/2010/06/100623123357.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) — Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) — Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) — Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) — Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins