Navigation Links
DNA-damage Test Could Aid Drug Development

In the daunting marathon that leads to successful drugs, promising drug candidates must pass toxicity tests before entering clinical trials. Researchers from Massachusetts Institute of Technology and Whitehead Institute have developed a cell culture test for assessing a compounds genetic toxicity that may prove dramatically cheaper than existing animal tests. This assay would allow genetic toxicity to be examined far earlier in the drug development process, making it much more efficient.

Like the current FDA-approved test, the new test looks for DNA damage in red blood cells formed in the bone marrow of mice. The precursors to red blood cells are handy for this because such cells normally lose their nucleus during the last stage of red cell formation, and DNA-damaged precursors generate red blood cells containing an easily detected 'micronucleus' consisting of fragments of nuclear DNA. Unlike the current procedure, which injects the compound into a live mouse, the new assay is a cell-culture system that could allow hundreds or thousands of tests to be performed from the bone marrow of a single mouse, and potentially from human bone marrow.

Joe Shuga, the graduate student in chemical engineering who developed the assay, is in the unusual position of being a graduate student in three labs, those of Professors Linda Griffith, Harvey Lodish (a Whitehead Member) and Leona Samson. 'We're all faculty in the Biological Engineering department, and collaborative projects like this are what the department was intended to do,' comments Griffith.

'This is an example of taking fundamental lab science and doing something useful with it,' says Lodish, whose lab has extensively studied the process by which red blood cells are generated. Shuga first worked with postdoctoral researcher Jing Zhang in the Lodish lab to adapt techniques from an established cell-culture system based on mouse fetal liver cells to create a new system based on adult red cell precursors from mouse bone marrow. Shuga patiently optimized the system, which allows the precursor cells to proliferate and differentiate in the normal way, dividing four or five times before losing their nucleus and becoming immature red blood cells.

Shuga then studied the way these developing cells reacted to three toxic DNA- damaging agents whose effects had been studied by Samsons lab, and found the results correlated well with results from the existing test. Additionally, he experimented with mutant mice created by Samsons lab that are deficient in certain DNA-repair systems. The bone marrow cells derived from these mice, and the cells cultured from that bone marrow, proved more sensitive to the toxic agents than were the cultured cells from normal mice, further confirming the results.

With the new assay, 'instead of testing one chemical and one dose in one animal, you'll be able to take one animal, get the bone marrow out and test a thousand different conditions,' Samson says. 'You'll be able to look in more detail at different doses given at different times in the cell differentiation process.'

'This is a much cheaper assay thats at least as predictive as previous assays,' emphasizes Griffith, 'and drug developers can afford to use it a lot earlier in the drug development process.' It also could help to avoid issues with animal testing. 'The European Union is trying to minimize animal testing,' Shuga points out. 'A ban on animal testing of cosmetic products goes into effect in 2009.'

Next steps in the research, which may be carried out by industry partners, will be to test the assay in rats and other organisms, and with a wide variety of other toxic chemicals.

'This research is the first stage in a new type of clinical drug toxicity test,' says Lodish. 'And although we haven't done it, you may be able to extend the technique to humans. Humans are the gold standard in that one wan ts an assay that directly predicts toxicity in humans, not animals, and you could obtain human bone marrow thats left over from medical procedures.'

'If you could change the micronucleus assay to have a human cell readout, that would be pretty amazing,' says Samson. Down the road, she suggests, such a test might offer a new way to examine how different individuals respond to chemotherapeutic agents.

'The presumption is that, for some biological processes, in vitro human models could be closer to in vivo human than in vivo mouse,' notes Shuga. 'That premise will be tested in coming years as new systems become available.'


'"/>




Related medicine news :

1. Lean Protein Could Be Key to Obesity Drugs
2. Nasal Spray Could Take Drugs Direct to Brain.
3. Nasal Spray Could Take Drugs Directly to Brain
4. Oxygen Usage During Exercise Could Indicate Heart Problems
5. Ultrasound Screening Could Improve The Outcome Of Critically ill Patients
6. Anger Could Be Linked To Weight Gain
7. A Seizure Late In Life Could be A Stroke Warning
8. New Findings Could Reduce The Extent Of Spinal Cord Injuries
9. Could There Be A Link Between Famine and Breast Cancer ?
10. Bone Marrow Cells Could Yield A New Lease of Life
11. New Hair in 15 Days Could Now Be A Possibility Say Researchers
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/25/2016)... D.C. (PRWEB) , ... June 25, 2016 , ... ... discuss health policy issues and applications at AcademyHealth’s Annual Research Meeting June 26-28, ... their work on several important health care topics including advance care planning, healthcare ...
(Date:6/25/2016)... Beach, CA (PRWEB) , ... June 25, 2016 , ... ... UCLA with Magna Cum Laude and his M.D from the David Geffen School of ... Diego and returned to Los Angeles to complete his fellowship in hematology/oncology at the ...
(Date:6/24/2016)... ... 24, 2016 , ... Those who have experienced traumatic events may suffer from ... avenues, such as drug or alcohol abuse, as a coping mechanism. To avoid this ... coping following a traumatic event. , Trauma sufferers tend to feel a range of ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... for accelerated orthodontic treatment. Dr. Cheng has extensive experience with all areas of ... AcceleDent, and accelerated osteogenic orthodontics. , Micro-osteoperforation is a revolutionary adjunct to ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Haute Beauty ... Barry M. Weintraub as a prominent plastic surgeon and the network’s newest partner. ... and the most handsome men, look naturally attractive. Plastic surgery should be invisible.” ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... June 24, 2016  Collagen Matrix, Inc., ("Collagen ... and manufacturing of collagen and mineral based medical ... that Bill Messer has joined the ... further leverage the growing portfolio of oral surgery, ... Bill joins the Collagen Matrix executive team ...
(Date:6/24/2016)... 2016 Research and Markets ... Electronics 2015-2025: Applications, Technologies, Forecasts" report to ... In-Mold Electronics, Smart Skin, Structural Health Monitoring, Composite ... Structural electronics involves electronic and/or electrical components and ... dumb structures such as vehicle bodies or conformally ...
(Date:6/24/2016)... DUBLIN , June 24, 2016 ... "The World Market for Companion Diagnostic Tests" report to ... World Market for Companion Diagnostics The World ... diagnostic and personalized medicine diagnostics. Market analysis in the report ... Diagnostics Test Market (In Vitro Diagnostic Kits) by Region (N. ...
Breaking Medicine Technology: