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La droga pudo ofrecer esperanza a la radiación y a las víctimas del cáncer

por Brendon Nafziger, DOTmed News Associate Editor | June 25, 2010

Eventually, Sharpless got to work with drug companies experimenting on a class of drugs used in cancer research, which appear to prevent some cancer cells from dividing. While the drug companies hope to use them against cancer, Sharpless realized they might have potential in combating the effects of acute radiation syndrome.

"Some of these compounds have a very nice property -- they will cause certain cells in the bone marrow, cause them to go to sleep, go out of the cell cycle," Sharpless said.

According to Sharpless, the drug works by locking cells in the non-dividing phase by inhibiting substances their division is dependent on, called cyclin-dependent kinase 4 and 6. Critically, say the researchers, these CDK 4 and 6 inhibitors are basically non-toxic, as blood-making bone marrow is one of the few cell types to depend on CDK 4 and 6 to divide.

"This class of agents didn't cause global blocks," Sharpless said. "You need proliferating cells. Inhibiting proliferation globally is bad. That's what chemotherapy does."

PREVENTING DIVISION

In the study published Wednesday, mice were exposed to lethal doses of whole-body radiation form either X-ray or gamma ray sources. The animals received about 7.5 - 8.5 Gy, a more than lethal dose.

Some of the mice were given CDK 4 and 6 inhibitors, dubbed PD0332991, developed and mostly supplied by Pfizer, and 2BrIC, synthesized by Otava Ltd., either before or up to 20 hours after radiation exposure.

The scientists followed the animals for about a month, as most will normally die within 28 days from radiation-induced bone marrow damage, Sharpless said.

At 7.5 Gy, all mice treated with the inhibitors survived, while nearly all untreated mice died. Still, the mice aren't immune to radiation: at 8.5 Gy, only about 13 percent of treated mice survived after 30 days (none of the untreated ones did).

And Sharpless said the drug couldn't protect against damage to the gut or lungs, as those cells don't depend on CDK 4 and 6 to cycle.

Nonetheless, the researchers found that the treatment protected nearly all blood lineages, including platelets, which no available therapy can do, Sharpless said.

The researchers also worked out the effects of the inhibitors in human cell lines, to show that the drug only acts on cells "addicted" to CDK 4 and 6 for their replication.

MASS DOSING

Important for its usefulness is that, as a small molecule drug, a pill, it doesn't require refrigeration and could be stockpiled easily, or carried around in ambulances.

Also, its low toxicity makes it appropriate for the kind of mass casualty accident or attack where first responders will have to give treatment to potentially hundreds, or thousands, of people without being able to gauge how much radiation they got.