Dr Huiling Xu, A/Prof Michael McKay
Peter MacCallum Cancer Centre
This project studies the role of an important gene in contributing to the radiation response in humans. It may lead to better radiotherapy outcomes and cancer cures.
Radiotherapy (RT) is employed in approximately half of all cancer patients. Most RT is delivered to a cancer-affected organ, unavoidably encapsulating normal tissues surrounding a tumour.
Optimal outcomes are a balance between normal tissue toxicity and tumour control. Identification of potential new mammalian radiation responsive genes/pathways therefore promises a better understanding of the effects of radiation on the majority of patients' normal tissues and tumours.
Rad21 is a gene present in all species and essential for proper partitioning of genetic materials into daughter cells during cell division. We generated mutant mice lacking one copy of Rad21 gene and found that mutant animals exhibited sensitivity considerably greater than controls when challenged with whole body radiation (WBR).
Our investigation further revealed that enhanced radiation sensitivity observed in mutant mice is the consequence of damage to the gastrointestinal tract (GIT) and blood forming (bone marrow) systems. We found evidence that Rad21 is required to repair DNA lesions in cells following radiation.
Rad21 deficiency resulted in inefficient repair of radiation-induced DNA damage, leading to enhanced radio-sensitivity. Our study thus shows that Rad21 gene dosage is critical for the radiation response not only at the cell and tissue levels but also after irradiation of the whole animals. This study is likely to have important implications in the understanding of acute radiation toxicity in normal tissues, especially of the GIT and bone marrow systems, observed during and after cancer RT.
Cancer Council Research Grant
$100,000 per annum