8-Hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most abundant oxidatively modified lesions in
DNA. Our previous study (Kondo et al, Free Radic. Biol.
Med., 27: 401-410, 1999) revealed that human
colorectal carcinoma cells are oxidatively stressed based on 8-OHdG determination. To elucidate 8-OHdG metabolism and its clinical significance in
colorectal carcinoma, we studied the 8-OHdG repair system in
DNA by measuring specific
lyase activity and hOGG1 expression using quantitative-competitive reverse transcription-PCR. In addition, we searched for the presence of mutations and single nucleotide polymorphisms of the hOGG1 gene by single-strand conformational polymorphism and sequencing analyses. It was found that 8-OHdG-specific
lyase activity and hOGG1 expression were significantly up-regulated in
carcinoma, and a proportional association between 8-OHdG levels and either 8-OHdG
lyase activity (r = 0.641, P < 0.05) or hOGG1 expression (r = 0.702, P < 0.05) was present. Whereas no difference was detected in the 8-OHdG level between early- and advanced-stage
cancer,
lyase activity (1.2-fold) and hOG1 expression (1.6-fold) were significantly increased in advanced-stage
cancer. No mutation was found in the 25
tumors examined. Three kinds of single
nucleotide polymor. phism were observed, including that of
codon 326 (Ser/Cys) in exon 7. However, there was no correlation between any of the three polymorphic patterns and either 8-OHdG level or
lyase activity. These results suggest that increased 8-OHdG levels in
colorectal carcinoma are attributed to increased formation and are maintained by induced 8-OHdG repair activity at appropriate high levels. Our results may offer a unique approach in the development of preventive and therapeutic interventions as well as new insights into the pathogenesis of
colorectal carcinoma.