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Small molecules in the blood might gauge radiation effects after exposure
By Dross at 2013-02-26 23:50
Small molecules in the blood might gauge radiation effects after exposure

Currently, doctors have no way to accurately measure damage to the body soon after a person is exposed to ionizing radiation.
It is therefore difficult to know whether a person is likely to suffer serious effects after an occupational or accidental exposure.
This animal study shows that radiation exposure alters the levels of certain small molecules in the blood, perhaps offering a reliable measure of damage to the body.
COLUMBUS, Ohio – Ohio State University cancer researchers have identified molecules in the bloodstream that might accurately gauge the likelihood of radiation illness after exposure to ionizing radiation.

The animal study, led by researchers at The Ohio State Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James), shows that X-rays or gamma rays alter the levels of certain molecules called microRNA in the blood in a predictable way.

If verified in human subjects, the findings could lead to new methods for rapidly identifying people at risk for acute radiation syndrome after occupational exposures or accidents such as the recent Fukushima Daiichi nuclear reactor incident. The microRNA markers might also help doctors plan radiation therapy for individual patients by taking into account how different people respond to radiation treatment, the researchers say.

The findings are reported in the journal PLOS ONE.

"Our paper reports the identification of a panel of microRNA markers in mice whose serum levels provide an estimate of radiation response and of the dose received after an exposure has occurred," says senior author Dr. Arab Chakravarti, chair and professor of Radiation Oncology, the Max Morehouse Chair in Cancer Research and co-director of the Brain Tumor Program.

"Accurate dose evaluation is critical for making medical decisions and for the timely administration of therapy to prevent or reduce acute and late effects."

The findings might also one day allow doctors to evaluate radiation toxicity during the course of therapy based on an individual's biology. "This would particularly benefit leukemia and lymphoma patients who receive total body irradiation in preparation for stem-cell transplantation," Chakravarti says.

First author Dr. Naduparambil Jacob, a research assistant professor in radiation oncology, noted that the study could be an important step in the development of biological dosimetry, or biodosimetry, a technology for identifying people at risk for acute radiation illnesses that develop within weeks of radiation exposure, and cancers and degenerative diseases that can occur months or years later.

"Biodosimetry is an emerging concept that could enable us to identify individuals who need immediate treatment after a radiation exposure and to better develop personalized radiation treatment plans for patients," Jacob says.

For this study, Chakravarti, Jacob and their colleagues evaluated dose-dependent changes in levels of 88 individual microRNAs in serum from mice after a single acute radiation exposure, and after fractionated doses of radiation that are typical of radiation treatment prior to stem-cell transplantation. Samples were collected from exposed and control animals 24 or 48 hours after exposure.

Key technical findings include:

After a one-time exposure, miRNA-150 showed a clear decrease over time with increasing radiation dose, with a drop of 30 percent after 24 hours and of 50 percent after 48 hours, even at the lowest exposure of one gray of radiation.
miRNA-200b and miRNA-762 showed increased levels after radiation exposure, with the changes more pronounced in animals receiving higher doses.
Animals receiving fractioned doses showed similar changes; e.g., miRNA-150 dropped about 50 percent after 24 hours in animals receiving 4 gray.



2 comments | 2293 reads

by gdpawel on Wed, 2013-02-27 05:14
Another area of interest that has been insufficiently explored is the possibility of using cell culture assays to predict a patient's response to radiation therapy.

A Chicago area oncologist, Robert Schrek, at one time applied the assay to the field of radiation therapy. He found that people vary greatly in the susceptibility of their cells to radiation.

One example was that some patients' leukemia cells could be destroyed with a mere two roentgens of radiation, while a few patients had cells that could withstand 1,000 roentgens.

Hinkley and Bosanquet of the Bath Cancer Research Unit reported the results of 61 CLL specimens from 40 patients showed profound inter-patient differences in the sensitivity of cells to radiation. Five patient specimens, which were radio-resistant in vitro, were from patients who were also resistant clinically to irradiation. Another patient who responded very well clinically was found to be extremely sensitive in a cell culture assay.

(Hinkley HJ, Bosanquet AG. The in vitro radiosensitivity of lymphocytes from chronic lymphocytic leukaemia using the differential staining cytotoxicity (DISC) assay. II-results on 40 patients. Int J Radiat Biol. 1992;61:111-121)

Comby, of the University of Caen also observed this relationship in B-cell CLL and predicted the utility of cell culture assays as a valuable clue to the selection of irradiation regimens for B-CLL patients and assessing the impact of radiation on tumor cell death. Investigation of correlations between in vitro radiation-induced apoptosis and the in vivo response to radiation therapy.

(Comby E, Andre I, Troussard X, et al. In vitro evaluation of B-CLL cells apoptotic responses to irradiation. Leuk Lymphoma. 1999;34:159-166)

I understand there are no cell culture assay labs in the world that are currently offering their tests before patients undergoing radiation treatment. It seems likely that adopting research into the use of cell culture assays for pre-screening radiation therapy could be very beneficial.

Differential Staining Cytotoxicity Assay (DiSC)

[url]http://www.ncbi.nlm.nih.gov/pubmed/21516414

by gdpawel on Mon, 2013-03-11 04:00
Kathy Boltz, PhD.

Molecules in the bloodstream that might accurately gauge the likelihood of radiation illness after exposure to ionizing radiation have been identified. This animal study shows that X-rays or gamma rays alter the levels of certain molecules called microRNA (miRNA) in the blood in a predictable way. If verified in human subjects, the findings could lead to new methods for rapidly identifying people at risk for acute radiation syndrome after occupational exposures or accidents such as the recent Fukushima Daiichi nuclear reactor incident.

"Our paper reports the identification of a panel of miRNA markers in mice whose serum levels provide an estimate of radiation response and of the dose received after an exposure has occurred," said senior author Arnab Chakravarti, MD, of The Ohio State University (OSU). "Accurate dose evaluation is critical for making medical decisions and for the timely administration of therapy to prevent or reduce acute and late effects."

The findings might also one day allow doctors to evaluate radiation toxicity during the course of therapy based on a patient's biology. "This would particularly benefit leukemia and lymphoma patients who receive total body irradiation in preparation for stem cell transplantation," Chakravarti said.

First author Naduparambil Jacob, PhD, also of OSU, noted that the study could be an important step in the development of biological dosimetry, or biodosimetry, a technology for identifying people at risk for acute radiation illnesses that develop within weeks of radiation exposure, and cancers and degenerative diseases that can occur months or years later. The study was published in PLOS ONE (2013; doi:10.1371/journal.pone.0057603).

"Biodosimetry is an emerging concept that could enable us to identify individuals who need immediate treatment after a radiation exposure and to better develop personalized radiation treatment plans for patients," Jacob said.

For this study, Chakravarti, Jacob, and their colleagues evaluated dose-dependent changes in levels of 88 individual miRNAs in serum from mice after a single acute radiation exposure, and after fractionated doses of radiation that are typical of radiation treatment prior to stem cell transplantation. Samples were collected from exposed and control animals 24 or 48 hours after exposure.

After a one-time exposure, miRNA-150 showed a clear decrease over time with increasing radiation dose. It dropped 30% after 24 hours and 50% after 48 hours, even at the lowest exposure of 1 gray of radiation. Levels of both miRNA-200b and miRNA-762 increased after radiation exposure, and the changes were more pronounced in the animals that received the higher doses. Changes were similar for animals that received fractionated doses, such that miRNA-150 dropped about 50% after 24 hours in animals receiving 4 gray.

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