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Bladder Tumor Contains Higher N7-Methylguanine Levels in DNA than Adjacent Normal Bladder Epithelium

¹ Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust; ² Centre for Occupational and Environmental Health, University of Manchester, Manchester, United Kingdom; ³ Institute of Graduate Studies and Research and ⁴ Department of Pathology, University of Alexandria, Alexandria, Egypt

Requests for reprints: Andrew C. Povey, Centre for Occupational and Environmental Health, University of Manchester, Humanities Building, Manchester M13 9PL, United Kingdom. Phone: 161-275-5232; Fax: 011-44-161-275-5595. E-mail: apovey{at}manchester.ac.uk

Schistosoma haematobium–infected patients are more likely to develop bladder cancer and be more exposed to carcinogenic N-nitroso compounds than uninfected patients. As N7-methylguanine is a marker of exposure to methylating agents of this type, we have measured N7-methyldeoxyguanosine 3'-monophosphate (N7-MedGp) by ³²P postlabeling. DNA was isolated from 42 paired normal and tumor tissue of Egyptians with bladder cancer. N7-MedGp was detected in DNA from 93% of the tumors and 74% of the normal bladder tissue samples. Adduct levels were highly variable and ranged from 0.04 to 6.4 and from 0.02 to 0.72 µmol/mol deoxyguanosine 3'-monophosphate (dGp) in tumor and normal DNA, respectively. N7-MedGp levels in normal and tumor DNA were highly correlated with one another (P = 0.007). The mean difference (95% confidence interval) in adduct levels between tumor and normal DNA was 0.21 (0.13-0.32) µmol/mol dGp and this was statistically significant (P < 0.001). The adduct ratio (tumor DNA/normal DNA) varied between 0.2 and 136 (median, 4.6). N7-MedGp levels were not associated with gender, age, or the presence of schistosomiasis. However, lower N7-MedGp levels were found in normal DNA from individuals lacking the GSTM1 gene (P = 0.03) but not the GSTT1 gene or in subjects with the Ile105Val GSTP1 polymorphism. These results show that exposure to methylating agents is widespread and suggest that such exposure may play a role both in tumor initiation and progression. (Cancer Epidemiol Biomarkers Prev 2006;15(4):740–3)