WASHINGTON -- Two studies funded by NASA and presented at the AACR Annual Meeting 2013 help explain why space radiation may increase the risk of colorectal cancer in humans.

The researchers, from Georgetown Lombardi Comprehensive Cancer Center, found that cosmic radiation impairs the ability of cells in the intestines of mice to eliminate oncogenic proteins, thus substantially increasing development of colorectal tumors.

The findings are important because they might provide a direction for researchers in designing strategies to protect space travelers against increased cancer risk, say the scientists, Shubhankar Suman, PhD, and Kamal Datta, MD. Both scientists are involved in a NASA Specialized Center of Research (NSCOR), directed by the Molecular Cancer Research Chair at Georgetown Lombardi, Albert Fornace Jr., MD.

"While there is no reliable estimate of colorectal cancer risk from space radiation exposure, we have shown that exposure to cosmic radiation causes markedly increased intestinal tumors in mice," says Datta, an assistant professor in the department of biochemistry and molecular & cellular biology.

"These findings have implications for the health of astronauts undertaking exploratory missions into outer space and for future space tourists," he says.

"Our objective is to develop a risk estimate based on mouse model studies and to identify molecular mechanisms contributing to it, so that we can develop strategies to protect astronauts during long duration space missions, such as one to Mars," says Fornace, director of the NASA program at Georgetown.

Both researchers used specialized mutant mice to study the effects of 56Fe radiation, a highly ionizing radiation prevalent in space. "This radiation is considered the greatest challenge for space exploration," says Datta. "It deposits higher amount of energy in the body than does the gamma-/x-rays causing relatively higher DNA damage. This is believed to increase carcinogenic risk in astronauts, although accurate risk estimates are not yet available."

Georgetown researchers also report that 56Fe radiation significantly increased colorectal cancer risk in mouse models of colorectal cancer through enhanced activity of beta-catenin, an oncogene that activates expression of pro-growth genes in the colon.

In his study (abstract #3600), Datta reports that tumor formation in mouse intestines after exposure to cosmic radiation, unlike after exposure to gamma radiation, was dose dependent.

"Sustained exposure during prolonged space missions such as a mission to Mars and lengthy stays at the International Space Station may cause significant cosmic radiation dose accumulation in astronauts and thus remains a long-term health concern of space exploration," says Datta.

In his study (abstract #428), Suman, a postdoctoral fellow in the department of biochemistry and molecular biology, report that cancer causing beta-catenin levels are increased because cosmic radiation reduces the cell's ability to tag beta-catenin proteins for destruction. That means intestinal cells cannot degrade this cancer causing protein allowing uncontrolled cell growth.

"Knowing how space radiation induces tumor formation will allow us to develop preventive strategies that target this specific signaling pathway," Suman says.

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The authors report having no personal financial interests related to the study.

About Georgetown Lombardi Comprehensive Cancer Center

Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute (grant #P30 CA051008), and the only one in the Washington, DC area. For more information, go to http://lombardi. georgetown. edu .

About Georgetown University Medical Center

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis - or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical Translation and Science Award from the National Institutes of Health.