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Study pinpoints protein that detects damage from radiation

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Small intestine tissue from mouse after high-dose X-ray radiation. Green fluorescence shows dying epithelial cells.

High doses of radiation from cancer treatment can cause severe damage to cells and tissues, resulting in injury to bone marrow and the gastrointestinal tract. The consequences can be fatal. Yet researchers do not fully understand how exposure to radiation triggers this damage at the molecular level.

Led by Yale professor of immunobiology Richard Flavell, an international team of researchers studied the radiation response using animal models. They identified a novel mechanism of radiation-induced tissue injury involving a protein called AIM2, which can sense double-strand DNA damage and mediate a special form of cell death known as pyroptosis.

They observed that in animals lacking AIM2, both the gastrointestinal tract and bone marrow were protected from radiation. While the role of AIM2 as a sensor that detects infectious threats to the body was known, this study is the first to describe the protein’s function in the detection of radiation damage to the chromosomes in the nucleus, said the researchers.

When a cell receives a high dose of radiation, the DNA is broken into pieces, which can be joined together again. However this aberrant rejoining of chromosomal fragments can lead to chromosomal abnormalities and cancer. Flavell and his team believe that when this chromosomal damage is inflicted, the AIM2 pathway is activated in order to kill the cell to avoid the deleterious consequences of these chromosomal translocations, such as those commonly seen in cancer cells.

For this reason, the cells that accumulate this chromosomal damage are dangerous to the person or animal and are therefore killed by this AIM2 pathway. This pathway is beneficial to the person or animal under normal circumstances because it eliminates dangerous cells, but when a high dose of radiation is given the pathway is detrimental because it leads to bone marrow and digestive tract injury.

These findings suggest that a drug that blocks or inhibits the AIM2 pathway could potentially limit the deleterious side effect of chemotherapy or radiotherapy on cancer patients, said the researchers.

Read the full paper in Science.

http://news.yale.edu/2016/11/10/study-pinpoints-protein-detects-damage-radiation

November 11, 2016 Posted by | radiation | , | Leave a comment

Russia, Japan Team Up to Study How Radiation Affects the Next Generation’s DNA

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Russia and Japan are set to team up to become leaders in transgenerational healthcare research, to help prevent the effects of nuclear catastrophes being passed genetically from one generation to the next indefinitely.

Both Russia and Japan have a stake in this research, given that both countries are still dealing with radiation exposure via the events in Nagasaki, Hiroshima, Fukushima and Chernobyl. “This research is extremely important in relation to future generations we are responsible for,” said Nomura Taisei, Radiation Biology and Medical Genetics Department Head at National Institute for Biomedical Research at Osaka University.

The professor was at the 15th Congress on Innovation Technologies in Pediatrics and Pediatric Surgery which was held in Moscow from October 25-27, making a report on trasngenerational healthcare. His report shines a light on how exposure to radiation is passed down through generations via DNA mutation.

When DNA is damaged, the consequences for future generations are serious.Birth abnormalities, developmental disorders, a weakened immune system, higher cancer risks, and numerous physical and mental disorders are all the result of these gene mutations passed down to future generations. While the effects of radiation exposure passing between generations has so far not been widely studied in humans, the effects on experimental animal subjects is more widely understood.

Professor Nomura’s experiments on mice proved that genetic effects of radiation exposure can cause genetic defects into the 58th generation. The problem is that Japan has very little data on radiation exposure on humans.

This is where Russia can help, through opening up their database on three tree generations of people: those who were exposed after the Chernobyl disaster, those who were exposed prenatally, and those whose parents were exposed before impregnation. Thus Russia and Japan can now conduct joint comparative research of the effects of radiation on animals and on humans applying the latest technologies.

The Head of Children’s Scientific and Practical Center of Radiation Protection, Larisa Naleva told Sputnik Japan about the importance of this Russian-Japanese research project.

“We assume that the phenomenon of radiation-induced genetic instability has significant effects not only on the health of exposed people but also on the health of their children, first of all, resulting in an increased cancer risk. We have already detected an increase of morbidity in the second generation of exposed people’s descendants and now we are studying the third generation. Today in Russia there are about 135 thousand children who have been exposed or are exposed to radiation to some extent,” said Naleva. By using Japan’s expertise, Naleva hopes that the health risk for subsequent generations of those who were exposed to radiation can be reduced. “And that is the goal of our collaboration with our Japanese colleagues,” she said.
https://sputniknews.com/society/201611021046998030-russia-japan-radiation-dna/

November 4, 2016 Posted by | radiation | , , , , , | 1 Comment

DNA damage, cancer caused by ionizing radiation identified

This UPI article was published on Sept. 13, 2016.
I added below the source of that UPI article, the study published on the sciences website “Nature” on Sept. 12, 2016.
This article is important, and should be seen by as many people as possible, as this scientific study will impact greatly the future of our anti-nuclear cause.
By establishing the genetic signatures of any cancer caused by ionizing radiation, any future denial from the nuclear lobby is now impossible. Those scientifically established signatures will also be extremely helpful in court for any future suit from radiation victims.

Researchers found mutational signatures left by radiation-caused changes to DNA, which may lead to better treatment of cancers.

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Researchers found mutational signatures which appear to indicate changes to DNA caused by exposure to ionizing radiation, which may allow doctors to better treat cancer caused by non-spontaneous mutations.

LONDON, Sept. 13 (UPI) — Though scientists have suspected ionizing radiation can cause cancer, experiments conducted in England are the first to show the damage it inflicts on DNA and may allow doctors to identify tumors caused by radiation.

In a study published in the journal Nature Communications, scientists showed the effects of gamma rays, X-rays and radioactive particles on DNA, deciphering patterns they think will help differentiate between spontaneous and radiation-caused tumors, allowing for better cancer treatment.

“To find out how radiation could cause cancer, we studied the genomes of cancers caused by radiation in comparison to tumors that arose spontaneously,” Dr. Peter Campbell, a researchers at the Wellcome Trust Sanger Institute, said in a press release. “By comparing the DNA sequences we found two mutational signatures for radiation damage that were independent of cancer type. We then checked the findings with prostate cancers that had or had not been exposed to radiation, and found the same two signatures again. These mutational signatures help us explain how high-energy radiation damages DNA.”

For the study, the researchers looked for mutational signatures in 12 cancer patients with radiation-associated second malignancies, and compared their tumors to 319 from patients not exposed to radiation.

The researchers found two mutational signatures they link to radiation. While one causes small deletions of DNA bases, the other — called a balanced inversion — includes two cuts to DNA, with the middle piece spinning around and rejoining in the opposite direction.

These mutations, especially balanced inversions, which do not happen naturally in the body, increase the potential for cancer to develop, the researchers say.

“This is the first time that scientists have been able to define the damage caused to DNA by ionising radiation,” said Adrienne Flanagan, a professor at the University College London Cancer Institute. “These mutational signatures could be a diagnosis tool for both individual cases, and for groups of cancers, and could help us find out which cancers are caused by radiation. Once we have better understanding of this, we can study whether they should be treated the same or differently to other cancers.”

http://www.upi.com/Health_News/2016/09/13/DNA-damage-cancer-caused-by-ionizing-radiation-identified/5151473765849/

Mutational signatures of ionizing radiation in second malignancies

« Ionizing radiation is a potent carcinogen, inducing cancer through DNA damage. The signatures of mutations arising in human tissues following in vivo exposure to ionizing radiation have not been documented. Here, we searched for signatures of ionizing radiation in 12 radiation-associated second malignancies of different tumour types. Two signatures of somatic mutation characterize ionizing radiation exposure irrespective of tumour type. Compared with 319 radiation-naive tumours, radiation-associated tumours carry a median extra 201 deletions genome-wide, sized 1–100 base pairs often with microhomology at the junction. Unlike deletions of radiation-naive tumours, these show no variation in density across the genome or correlation with sequence context, replication timing or chromatin structure. Furthermore, we observe a significant increase in balanced inversions in radiation-associated tumours. Both small deletions and inversions generate driver mutations. Thus, ionizing radiation generates distinctive mutational signatures that explain its carcinogenic potential. »

http://www.nature.com/ncomms/2016/160907/ncomms12605/full/ncomms12605.html

September 14, 2016 Posted by | radiation | , , | Leave a comment

Aspects of DNA Damage from Internal Radionuclides

Christopher Busby1

 

More on http://www.intechopen.com/books/new-research-directions-in-dna-repair/aspects-of-dna-damage-from-internal-radionuclides

May 19, 2016 Posted by | Nuclear | , , | Leave a comment