Genes identified that contribute to radiation resistance

A team of researchers from the University of Wisconsin have identified 46 genes in Escherichia coli that are necessary for its survival at exceptionally high levels of radiation. The paper appears ahead of print in theJournal of Bacteriology.

“The research has revealed new pathways of cellular self-repair, including DNA pathways that in humans that may help protect us from cancer,” says corresponding author Michael M. Cox.

High doses of radiation are deadly not only to humans, plants, and animals, but to microbial cells generally. Nonetheless, certain bacteria, notably Deinococcus radiodurans, are highly resistant to high level radiation. E. coli normally lacks such radiation resistance, but resistant strains were developed by subjecting them to increasing levels of radiation, and harvesting the survivors of each generation.

The 46 genes did not result from the mutations created under high radiation levels, but rather genes that exist in the normal, wild-type E. coli. The results reinforce the notion that survival after high doses of ionizing radiation does not depend on a single mechanism or process, but instead is multifaceted.

“We established a role for genes involved in processes as diverse as central metabolism and the synthesis and maintenance of the cell wall in radiation survival,” says Cox. “Perhaps most important, we identified eight genes of unknown function that play substantial roles in radiation survival.”

The benefits of this research and its progeny could be substantial, says Cox. “Our understanding of how cells deal with ionizing radiation is very rudimentary. Our work provides an expanded map of the cellular functions that are most directly involved in ameliorating the effects of ionizing radiation. It has revealed some potentially new pathways by which cells repair their DNA and more generally repair their cellular proteins and other components after exposure to high levels of radiation.”

One gene, previously of unknown function, has a role in repairing double strand breaks in DNA. “The gene is related to a human gene called XPB, and it may help elucidate some key DNA repair pathways in humans that help protect us from cancer,” says Cox.

http://www.medicalnewstoday.com/releases/279931.php

 

 

 

Nanoparticles used to enhance chemotherapy

University of Georgia researchers have developed a new formulation of cisplatin, a common chemotherapydrug, that significantly increases the drug’s ability to target and destroy cancerous cells.

Cisplatin may be used to treat a variety of cancers, but it is most commonly prescribed for cancer of the bladder, ovaries, cervix, testicles and lung. It is an effective drug, but many cancerous cells develop resistance to the treatment.

Shanta Dhar, assistant professor of chemistry in the UGA Franklin College of Arts and Sciences, and Rakesh Pathak, a postdoctoral researcher in Dhar’s lab, constructed a modified version of cisplatin called Platin-M, which is designed to overcome this resistance by attacking mitochondria within cancerous cells. They published their findings recently in the Proceedings of the National Academy of Sciences.

“You can think of mitochondria as a kind of powerhouse for the cell, generating the energy it needs to grow and reproduce,” said Dhar, a member of the UGA Cancer Center and principal investigator for the project. “This prodrug delivers cisplatin directly to the mitochondria in cancerous cells. Without that essential powerhouse, the cell cannot survive.”

Sean Marrache, a graduate student in Dhar’s lab, entrapped Platin-M in a specially designed nanoparticle 1,000 times finer than a human hair that seeks out the mitochondria and releases the drug. Once inside, Platin-M interferes with the mitochondria’s DNA, triggering cell death.

Dhar’s research team tested Platin-M on neuroblastoma – a cancer commonly diagnosed in children-that typically originates in the adrenal glands. In preliminary experiments using a cisplatin-resistant cell culture, Platin-M nanoparticles were 17 times more active than cisplatin alone.

“This technique could become a treatment for a number of cancers, but it may prove most useful for more aggressive forms of cancer that are resistant to current therapies,” said Pathak.

Both Dhar and Pathak caution that their experimental results are preliminary and they must do more work before Platin-M enters any clinical trials. However, their early results in mouse models are promising, and they are currently developing safety trials in larger animals.

“Cisplatin is a well-studied chemotherapy, so we hope our unique formulation will enhance its efficacy,” said Dhar, who is also a member of UGA’s Nanoscale Science and Engineering Center, Center for Drug Discovery, and Regenerative Bioscience Center. “We are excited about these early results, which look very promising.”

 

http://www.medicalnewstoday.com/releases/279303.php

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