Our research will help us to better understand how radiotherapy causes damage to the body and this may allow us to develop new treatments to heal radiation injury.

In humans with cancer, radiotherapy is used to kill cancerous cells. This treatment uses ionizing radiation which is aimed directly at the cancer however, it can also damage healthy cells in the area of the body surrounding the cancer. In patients with cancer of the head and neck, the salivary glands, which produce saliva in the mouth, can be damaged as a result of radiotherapy. If these glands are damaged the patients can suffer with chronic dry mouth which is extremely uncomfortable and greatly effects the patients quality of life.

What animals will be used in your research?

In our research, we use mice that have been bred for use in scientific research. Some of the mice will have had their DNA altered for a specific purpose and are known as genetically modified mice.

Why do you need to use animals? Is there no alternative?

Organs in the body are highly complex and are made up of different cells that work together to allow the specialised function of that organ. These organs and cells interact with other body systems for example blood in the circulation and nerve cells that are part of the nervous system.

For our research we need to be able to study different cells in body and how they communicate with other cells to better understand how regeneration in the body occurs and what goes wrong when regeneration does not happen following radiotherapy. We cannot replicate the complex interactions between cells in a culture grown outside of the body in a way that allows us to study the impact of radiotherapy on different types of cells. So, currently there are no viable alternatives to using animals in this type of research.

How many animals will you use?

We will use approximately 3000 mice per year over the course of five years, this includes mice that have been produced in breeding as well as mice that are used for collecting salivary glands and mice that are given a radiation injury.

How will you make sure that you use the minimum number of animals?

We want to be able to use the smallest number of mice in our research. Our research is carefully planned so that the correct number of mice are bred for purpose and we use statistical tests to work out the number of mice we need to make sure our results are reliable but that the smallest number of mice are used.

What procedures will the animals be involved in?

We will treat mice with gamma radiation, which is the same type of radiation used to treat cancer patients, to their head and neck area, the rest of their bodies will be shielded from the radiation by using a lead shield. Gamma radiation will affect the mice in a similar way as radiotherapy affects patients with cancer. Gamma radiation and radiotherapy damage healthy cells as well as cancer cells, we want to study how cells recover after being exposed to radiation.

We will carry out surgery on some mice to remove part of the salivary glands. This is similar to operating on patients to remove a cancerous tumour.

In some mice, we will use a syringe to inject new cells (a cell transplant) into the salivary glands that have been damaged by gamma radiation. By doing this, we will be able to learn whether a cell transplant will help the salivary gland grow again (regenerate).

In addition, we use mice that have had their DNA altered. In these mice cells of interest are labelled with a fluorescent ‘tag’, this allows us to see the cells and isolate them. We can also remove a gene from a particular family of cells so that we can understand the role the gene plays.

What is the expected harm to the animals and how will any harm be limited?

The majority of our mice are used for breeding or are bred and humanely killed for the collection of body tissues or cells for further analysis. They do not undergo an experimental procedure as is defined under the law and the impact to the animal is minimal which is known as ‘subthreshold’ severity.

The mice that are exposed to radiotherapy or have surgery to remove the salivary glands will experience some suffering associated with these procedures. This is assessed usually as being at a ‘moderate’ level of severity.

Harms to the mice are limited by giving the mice pain relief following surgery or radiation injury and by monitoring their health carefully during experiments. Animals that have had surgery sometimes scratch at their stitches and surgical wounds occasionally open up and must be re-stitched. The radiotherapy injury and removal of salivary glands can result in dry mouth, this will be alleviated with wet food that is easy for the mice to eat so they do not lose weight or become dehydrated.

The University works hard to encourage a ‘Culture of Care’ within our animal facilities. All mice will be looked after daily by experienced animal technicians and advice and care from veterinary staff is available round-the-clock. If the mice appear to be in pain or distress they will be humanely killed.

What are the expected benefits of this research?

a. Both short- and long-term benefits

The short-term benefits of our research will be a better understanding of how different cells communicate during organ regeneration and if any of these cells are missing or altered in situations when regeneration cannot happen. The long-term benefits of our research involve the possibility of finding drugs that can improve regeneration or test if cell transplantation can regenerate an injured organ.

b. Benefits of this research specifically as well as in the broader implications of the research

Scientific research, like our research, is essential to improve the lives of cancer patients after they have had intense treatment, such as radiotherapy. The findings from research like ours may have further reaching implications for other human diseases with no cure where organ regeneration may help, but where currently organ transplant is the only option to prolong life such as liver and lung disease.

Regenerating salivary glands after injury due to radiotherapy for cancer / Animal Research by blogadmin is licensed under a Creative Commons Attribution CC BY 3.0