Research Papers:

Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour

Anna Kovalchuk, Richelle Mychasiuk, Arif Muhammad, Shakhawat Hossain, Slava Ilnytskyy, Abhijit Ghose, Charles Kirkby, Esmaeel Ghasroddashti, Olga Kovalchuk _ and Bryan Kolb

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Oncotarget. 2016; 7:4385-4398. https://doi.org/10.18632/oncotarget.6596

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Anna Kovalchuk1, Richelle Mychasiuk1, Arif Muhammad1, Shakhawat Hossain1, Slava Ilnytskyy2, Abhijit Ghose3, Charles Kirkby3,4, Esmaeel Ghasroddashti3,4, Olga Kovalchuk2,5, Bryan Kolb1,5,6

1Department of Neuroscience, University of Lethbridge, Lethbridge, AB, Canada

2Department of Biological Sciences, University of Lethbridge, Lethbridge, AB, Canada

3Jack Ady Cancer Center, Alberta Health Services, Lethbridge, AB, Canada

4Department of Physics and Astronomy and Department of Oncology, University of Calgary, Calgary, AB, Canada

5Alberta Epigenetics Network, Calgary, AB, Canada

6Canadian Institute for Advanced Research, Toronto, ON, Canada

Correspondence to:

Bryan Kolb, e-mail: [email protected]

Olga Kovalchuk, e-mail: [email protected]

Keywords: radiation therapy, brain, neuroanatomy, behaviour, gene expression

Received: November 23, 2015     Accepted: November 24, 2015     Published: December 15, 2015


Radiation therapy can not only produce effects on targeted organs, but can also influence shielded bystander organs, such as the brain in targeted liver irradiation. The brain is sensitive to radiation exposure, and irradiation causes significant neuro-cognitive deficits, including deficits in attention, concentration, memory, and executive and visuospatial functions. The mechanisms of their occurrence are not understood, although they may be related to the bystander effects.

We analyzed the induction, mechanisms, and behavioural repercussions of bystander effects in the brain upon liver irradiation in a well-established rat model.

Here, we show for the first time that bystander effects occur in the prefrontal cortex and hippocampus regions upon liver irradiation, where they manifest as altered gene expression and somewhat increased levels of γH2AX. We also report that bystander effects in the brain are associated with neuroanatomical and behavioural changes, and are more pronounced in females than in males.

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