Antioxidant Genes Found to Protect Against Intestinal Cancer

City of Hope
Tuesday, 10 February 2004

A new study has found that the presence of two antioxidant genes that neutralize the damaging effects of oxygen byproducts protect against the onset of intestinal cancer, a disease that is diagnosed in about 5,300 people per year in the United States.

While oxygen is essential to life, oxidation of cells and tissues through their byproducts can cause damage that contributes to the development of cancer and heart disease. According to a study published in the current issue of the journal Cancer Research, City of Hope Cancer Center researchers found that turning off the antioxidant genes Gpx-1 and Gpx-2 that are found in the intestine, leads to chronic inflammation that can cause cancer. The study suggests that these antioxidant genes protect against the effects of inflammation produced by bacteria.

In the study, laboratory mice deficient in GPX enzymes, a type of protein produced by cells to protect against oxidative stress, experienced severe ileocolitis, an inflammatory bowel disease that can lead to cancer, unless they were kept germ-free. One of the mouse colonies, which harbored several species of a certain bacteria, the enterohepatic Helicobacter, had a tumor rate two-and-a-half times that of a "cleaner" colony without such bacteria, and a germ-free GPX-double knock-out (both genes turned off) colony had virtually no tumors.

"This study suggests that these enzymes play an important role in defending the intestines from the side effects of bacterial invasion," said Fong-Fong Chu, Ph.D., City of Hope Assistant Research Professor.

H. hepaticus, one of the enterohepatic Helicobacter bacteria found in the "dirty" colony, is known to contribute to the onset of ileocolitis and colon cancer in mice with severe immune-deficiency. Whether H. hepaticus is associated with human inflammatory bowel disease and colon cancer has not been established, Dr. Chu said. Since these GPX-double knockout mice do not have any apparent immune defect, it is important to demonstrate that H. hepaticus is a pathogen to GPX-double knockout mice and to relate its pathogenic activity in humans.

"We suspect that colonization of these bacteria activates epithelial cells by generating reactive oxygen species in cells, and only those humans or mice deficient in an antioxidant defense system will launch an unchecked inflammatory response, which may cause more damage to host cells and result in intestinal cancer," added Dr. Chu.

The City of Hope research team also included R. Steven Esworthy, Ph.D., senior research fellow; James H. Doroshow, M.D., chair, Division of Medical Oncology and Therapeutics Research; Peiguo G. Chu, M.D., staff pathologist, Department of Anatomic Pathology; Jeffery A. Longmate, Ph.D., associate professor, Division of Information Sciences; Sharon Wilczynski, M.D., Ph.D., staff pathologist, Department of Anatomic Pathology; and from the University of Oklahoma Health Science Center, Mark M. Huycke, M.D.

For more information, or to contact City of Hope, see their website at: www.cityofhope.org