Navigation Links
Drug mitigates toxic effects of radiation in mice

CHAPEL HILL, N.C. -- 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 today 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.


Contact: Ellen de Graffenreid
University of North Carolina School of Medicine

Related medicine news :

1. Ghrelin mitigates liver fibrosis in animal models; regulates human fibrosis
2. Students Target Toxic School Supplies
3. Pharmaceutical companies provide EPA 100 drugs to help predict toxicity
4. Second-hand smoke toxicity in cars: Myth into fact
5. Best Selling, Non Toxic Skin Brightener Does the Job Using Safe, Healthy Ingredients and Introduces New Anti Aging Ingredients
6. Transplant drug preserves kidneys, avoids toxicity
7. Popular nanoparticle causes toxicity in fish, study shows
8. Accelerated radiation therapy reduces toxicity in patients with advanced head and neck cancers
9. WuXi PharmaTech Receives AAALAC Accreditation for Suzhou Toxicology Facility
10. Toxic Construction Dust in Luxury New York Apartments Endangers Health, Angers Accident Attorneys Like David Perecman
11. 3 brain diseases linked by toxic form of same neural protein
Post Your Comments:
(Date:12/1/2015)... ... December 01, 2015 , ... McLean, VA., December 1, ... fixed price per sprint agile development contract to support the National Geospatial-Intelligence Agency's ... years, provides software engineering, infrastructure, as well as operations and sustainment support to ...
(Date:12/1/2015)... Auburn, CA (PRWEB) , ... December 01, 2015 ... ... software and clinical solutions for the care management and population health arenas, is ... on providing clinical and cost containment services, has successfully implemented the ACUITY Complete ...
(Date:12/1/2015)... Park, CA (PRWEB) , ... December 01, 2015 , ... ... (XTC) has selected 10 semi-finalists to head to Las Vegas for CES 2016, the ... judges including CEO of Consumer Technology Association Gary Shapiro, Founding Partner of Pacific Investments ...
(Date:12/1/2015)... ... , ... With FCPX Overlay: Grit , users can apply a grit ... are truly endless, all with a click of a mouse. Each user has full ... depth of field and more, all within Final Cut Pro X. , With FCPX ...
(Date:12/1/2015)... ... December 01, 2015 , ... ... as a Modern Man for 2015. , Angeleno Magazine is a division ... States. Established in 1994, Modern Luxury includes more than 50 magazine titles across ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... Ohio , Dec. 1, 2015 ... to its GeneSight® Psychotropic test giving healthcare providers an ... medication decisions for patients suffering from depression, anxiety, ... other behavioral health conditions. i ... --> With the addition of two ...
(Date:12/1/2015)... 2015 --> ... "Nucleic Acid Labeling Market by Product (Reagents & Kits, ... In Vitro Transcription, Reverse Transcription, End Labeling), by Region ... global market is expected to reach USD 1,925.7 Million ... at a CAGR of 8.65%. Browse 77 ...
(Date:12/1/2015)... , Dec. 01, 2015 ... the "Veterinary Equipment and Disposables Market by ... report to their offering. --> ... "Veterinary Equipment and Disposables Market by product, ... report to their offering. --> Research ...
Breaking Medicine Technology: