Active Voice: Obesity and Exercise Influence Late Effects of Radiation Exposure in Model of Cancer Survivorship
By Michael De Lisio, Ph.D.

Michael De Lisio, Ph.D.
Cancer incidence continues to rise, with approximately 40% of men and women expecting to receive a cancer diagnosis in their lifetime. The good news is that improvements in early detection and therapy have resulted in a steady increase in cancer survivorship. Indeed, it is expected that by 2026 there will be more than 20 million cancer survivors in the U.S. This increase in survivorship has created a new problem: How to prevent and manage the long-term, detrimental health effects of cancer therapy.

Most cancer survivors have been treated with radiation therapy. Epidemiological and experimental evidence has shown us that radiation exposure dramatically increases one’s risk of developing secondary malignancies. Blood cancers are some of the most common cancers to develop following radiation exposure. In addition, radiation exposure can lead to long-term inhibition of the immune system and persistent inflammation. One remaining unknown consequence, however, is whether certain patient characteristics can influence the effects of radiation on the blood system.

In our study, as presented in the June 2019 issue of Medicine & Science in Sports & Exercise® (MSSE), my colleagues and I investigated the effects of obesity and exercise training on blood system recovery following radiation exposure in mice. These lifestyle factors are particularly relevant as most cancer survivors are obese and physically inactive. Therefore, obese and lean mice were either entered into an exercise training program or remained sedentary. We used an exercise program that included elements advocated in ACSM’s Roundtable on Exercise Guidelines for Cancer Survivors. All mice were exposed to a dose of radiation sufficient to damage the blood system but non-lethal. Since the immune system and blood cancers develop in the bone marrow, we collected bone marrow samples to evaluate markers of blood/immune system regeneration and potential mediators responsible for these effects.

We were excited to find that exercise training resulted in a higher content of blood-forming stem cells and remodeled the environment within the bone marrow in a manner that supports blood/immune system regeneration. On the other hand, obesity had the opposite effect—reducing the number of blood-forming stem cells and inducing changes within the bone marrow that inhibit blood/immune regeneration. Further, we identified five proteins that were differentially regulated between the obese and exercise conditions that may explain the different responses between these two conditions and provide targets or biomarkers for future therapies.

Since exercise appeared to improve blood-forming stem cell development, we wanted to investigate whether exercise had similar effects on leukemia cells. We determined that factors within the bone marrow of exercise-trained mice did not increase leukemia growth in vitro. However, factors within bone marrow of obese mice did increase leukemia growth in vitro.

Together, our findings suggest that exercise can improve blood/immune cell regeneration without also enhancing leukemia cell growth. On the other hand, obesity reduces blood/immune cell regeneration while enhancing leukemia cell growth. Our findings in mice provide important early evidence to support the development of exercise interventions for long-term cancer survivors. Furthermore, they identify individuals with obesity as a population with increased risk for long-term complications.

About the author:
Michael De Lisio, Ph.D., is an associate professor of human kinetics and cellular and molecular medicine at the University of Ottawa in Ontario, Canada. His research focuses on the role of exercise and diet on regulating stem cell interactions with their local environment in chronic disease. He has been a member of ACSM since 2012.

Viewpoints presented in SMB commentaries reflect opinions of the authors and do not necessarily represent positions or policies of ACSM. Active Voice authors who have received financial or other considerations from a commercial entity associated with their topic, must disclose such relationships at the time they accept an invitation to write for SMB.