Abstract Molecular pathways that play a role in the development of colorectal cancer involve multiple genetic changes in cancer-related genes that may be caused by overproduction of reactive oxygen species (ROS) including free radicals. Various types of ROS are capable of damaging DNA and other biomolecules. Increased formation of ROS can contribute to genetic instability and promote the development of malignancy. These facts led us to hypothesize that oxidatively induced DNA damage may accumulate in colorectal cancer patients. To test this hypothesis, we investigated oxidatively induced DNA damage in colon and rectum tissues of cancer patients in comparison with their normal paired tissues. DNA was isolated from 51 colorectal cancer tissues. The levels of oxidatively induced DNA lesions such as 4,6-diamino-5-formamidopyrimidine (FapyAde), 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyGua), 8-hydroxyguanine (8-OH-Gua) and (5′S)-8,5′-cyclo-2′-deoxyadenosine (S-cdA) were measured by gas chromatography/isotope-dilution mass spectrometry and liquid chromatography/isotope-dilution mass spectrometry. We found that the level of 8-OH-Gua, FapyAde and FapyGua were significantly lower in cancer tissues than those in paired normal tissues (p=0.002, p=0.019 and p=0.005, respectively), whereas the S-cdA levels showed no significant difference between both tissues. These DNA base damages correlated with clinical and pathological data such as tumor location, tumor stage, gender and perineural invasion. The low levels of DNA base damage in tumor tissues when compared to their normal counterparts suggest an increase in DNA repair capacity in malignant tumors that may contribute to the resistance to therapeutic agents. This finding may lead to development of new therapeutic approaches. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1496.