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

2006; American Association for Cancer Research; Volume: 15; Issue: 4 Linguagem: Inglês

10.1158/1055-9965.epi-05-0813

1538-7755

Abir A. Saad, Peter J. O’Connor, Mostafa H. Mostafa, Nabila Metwalli, Donald P. Cooper, Geoffrey P. Margison, Andrew C. Povey,

Bladder and Urothelial Cancer Treatments

Abstract 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)