The Greater Oxidative Environment of the Colon than the Small Intestine may Explain the Difference in Cancer Susceptibility

Robert C. Burghardt, Ph.D.; Raymond J. Carroll, Ph.D.; and Joanne R. Lupton, Ph.D.
Center for Environmental and Rural Health
Texas A&M University
P30ES09106

Background: Colorectal cancer cases may outnumber cancer cases in the small intestine by as many as twenty-eight to one despite the fact that the small intestine has three times the surface area of the colon. The presence or absence of bacterial microflora and differences in the rate of cell turnover have been examined, but these differences provide incomplete explanations for the variation in cancer susceptibility. One possibility that has not been well characterized is the difference in the oxidative environments of the two tissues.

DNA damage resulting from reactive oxygen species (ROS) is a consequence of oxidative stress. Several oxidative DNA adducts have been implicated in the carcinogenic process. Oxidative stress results when antioxidant capability is exceeded by pro-oxidant concentration. This environment can result both from increased ROS production as well as impaired removal of ROS by antioxidant defenses.

Advance: This study examined base-line and induced ROS generation, antioxidant enzyme activity and oxidative DNA damage. Base-line ROS and antioxidant enzyme activities in the colon were higher than those observed in the small intestine. During induced oxidative stress, DNA adducts in the colon exceeded levels in the small intestine along with increased ROS concentration.

Implication: These data suggest that the greater rates of cancer occur in the colon because it responds to oxidative stress less effectively than the small intestine. The results show that the colon generates more ROS than the small intestine despite greater antioxidant enzyme activity. As oxidative damage has been implicated in the carcinogenic process, these results may help to explain the difference in cancer incidence between the colon and the small intestine. Further investigation by these and other researchers of the differences in these two tissues and their relation to cancer susceptibility may contribute to a greater understanding of the pathogenesis and possibly the future prevention of colon cancer.

Citation: Sanders LM, Henderson CE, Hong MY, Barhoumi R, Burghardt RC, Carroll RJ, Turner ND, Chapkin RS, Lupton JR. Pro-oxidant environment of the colon compared to the small intestine may contribute to greater cancer susceptibility. Cancer Lett. 2004 May 28;208(2):155-61.