X-ray-free electron laser reveals radiosensitizing effects at molecular level

June 17, 2016

While the effect of radiosensitizing molecules in radiation-based cancer therapies has been known for a long time, the exact molecular mechanisms behind it - the capacity of the radiosensitizer to locally augment the radiation damage to tumor cells by intratumoral administration of the agent - are yet to be deciphered.

However, an international team of researchers has illustrated how the molecule breaks apart and what ionic fragments are formed via the breakage of the molecular edifice shortly after the ionization, thus shedding light on the role of energetic ions in the initiation of damaging reactions.

The experiment took place at SACLA, an X-ray free electron laser facility in Japan. Its X-ray pulses are so bright and so brief that they have the ability to strip atomic nuclei, removing so many electrons from the targeted molecules, which then blow up within a tiny fraction of a second. The team succeeded at measuring kinetic energies and directions of the ionic fragments ejected from 5-iodouracil - a nucleobase analogue molecule of biological relevance, whose radiosensitizing effect has been known for a long time. The measurements were fully reproduced by theoretical modelling.

This joint effort of experimental and theoretical investigations, published in the top APS journal Physical Review X, also to be published in RSC's Faraday Discussions, gives clear evidence of the local production of a 'radiation soup' consisting of energetic ions, whose local damage effect adds to that of the genotoxic low energy electrons generated by electronic relaxation cascading mechanisms.

"We expect that the production of 'radiation soup' will contribute to the general understanding of how radiosensitizers work, and hope it will inspire the design of novel radiosensitizing drugs," says Kiyonobu Nagaya of Kyoto University, the lead author of the articles.

"The present study also clearly indicates that at the very early stages of the molecular dynamics following the interaction with the X-ray free electron laser radiation, only hydrogen atoms have time to move significantly, while the bonds between the heavier atoms elongate only slightly," says Kiyoshi Ueda of Tohoku University, who conceived the present study as a principal investigator. "This result validates the methodology for single-shot diffractive imaging of bio-macromolecules by the X-ray free electron laser as a reliable tool."

The result was achieved by an international team of researchers from Japan (Tohoku University, Kyoto University, Hiroshima University, Hiroshima Institute of Technology, Hokkaido University, RIKEN Spring-8 center, JASRI), Finland (University of Turku), United States of America (Kansas State University), France (Synchrotron SOLEIL), China (Beihang University, SARI, SINAP), Korea (POSTECH), and Romania (ELI-NP / IFIN-HH).
-end-
Contact:

Prof. Kiyoshi Ueda
Institute of Multidisciplinary Research for Advanced Materials,
Tohoku University, Sendai 980-8577, Japan
Email: ueda@tagen.tohoku.ac.jp
Phone: +81-22-217-5481

Dr. Kiyonobu Nagaya
Department of Physics, Kyoto University, Kyoto 606-8502, Japan
Email: nagaya@scphys.kyoto-u.ac.jp
Phone: +81-75-753-3772

Prof. Edwin Kukk
Department of Physics and Astronomy, University of Turku, Turku, FI-20014, Finland
Email: ekukk@utu.fi
Phone :+358-2-333-6089

Dr. Christophe Nicolas
Synchrotron Soleil, Saint-Aubin, BP 48, FR-91192 Gif-sur-Yvette Cedex, France
Email: christophe.nicolas@synchrotron-soleil.fr
Phone :+33-1-60-35-96-92

Dr. Catalin Miron (CS1)
Extreme Light Infrastructure - Nuclear Physics (ELI-NP),
"Horia Hulubei" National Institute for Physics and Nuclear Engineering,
30 Reactorului Street, RO-077125 Ma?gurele, Jud. Ilfov, Romania
Email: catalin.miron@eli-np.ro
Phone : +40-733-478-778

Tohoku University

Related Radiation Articles from Brightsurf:

Sheer protection from electromagnetic radiation
A printable ink that is both conductive and transparent can also block radio waves.

What membrane can do in dealing with radiation
USTC recently found that polymethylmethacrylate (PMMA) and polyvinyl chloride (PVC) can release acidic substance under γ radiation, whose amount is proportional to the radiation intensity.

First measurements of radiation levels on the moon
In the current issue (25 September) of the prestigious journal Science Advances, Chinese and German scientists report for the first time on time-resolved measurements of the radiation on the moon.

New biomaterial could shield against harmful radiation
Northwestern University researchers have synthesized a new form of melanin enriched with selenium.

A new way to monitor cancer radiation therapy doses
More than half of all cancer patients undergo radiation therapy and the dose is critical.

Nimotuzumab-cisplatin-radiation versus cisplatin-radiation in HPV negative oropharyngeal cancer
Oncotarget Volume 11, Issue 4: In this study, locally advanced head and neck cancer patients undergoing definitive chemoradiation were randomly allocated to weekly cisplatin - radiation {CRT arm} or nimotuzumab -weekly cisplatin -radiation {NCRT arm}.

Breaking up amino acids with radiation
A new experimental and theoretical study published in EPJ D has shown how the ions formed when electrons collide with one amino acid, glutamine, differ according to the energy of the colliding electrons.

Radiation breaks connections in the brain
One of the potentially life-altering side effects that patients experience after cranial radiotherapy for brain cancer is cognitive impairment.

Fragmenting ions and radiation sensitizers
The anti-cancer drug 5-fluorouracil (5FU) acts as a radiosensitizer: it is rapidly taken up into the DNA of cancer cells, making the cells more sensitive to radiotherapy.

'Seeing the light' behind radiation therapy
Delivering just the right dose of radiation for cancer patients is a delicate balance in their treatment regime.

Read More: Radiation News and Radiation Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.