8-oxodeoxyguanosine-triphosphate and Inflammation

Dextran sodium sulfate (DSS) given in drinking water can induce colonic inflammation and produce colorectal tumors in rodents, although it is not directly genotoxic. The hypothesis that DSS can produce free radicals and induce oxidative DNA damage in colonic mucosa has been tested. In rats fed for 2 days with water containing 3% and 6% DSS, colonic inflammation manifestations were recorded and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), a major biomarker of oxidative DNA damage, was assayed in colonic mucosa. As compared with control rats given pure water, inflammatory manifestations were seen in rats given DSS. At the same time, 8-oxodGuo levels in colonic mucosa were doubled (P < 0.001). These results suggest that formation of oxidative DNA damage in colonic mucosa depends on inflammation and maybe on the production of reactive oxygen species. This study shows that DSS can induce oxidative DNA damage within only 2 days, which could explain in part its carcinogenic properties.

Topics: Animals; Biomarkers; Colon; Colonic Diseases; Deoxyguanine Nucleotides; Dextran Sulfate; DNA Damage; Dose-Response Relationship, Drug; Female; Inflammation; Intestinal Mucosa; Occult Blood; Oxidative Stress; Rats; Rats, Inbred F344