Bladder tumor contains higher N7-methylguanine levels in DNA than adjacent normal bladder epithelium.
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 (32)P 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 micromol/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) micromol/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.
Saad
Abir A
AA
Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester.
O'Connor
Peter J
PJ
Mostafa
Mostafa H
MH
Metwalli
Nabila E
NE
Cooper
Donald P
DP
Margison
Geoffrey P
GP
Povey
Andrew C
AC
D001424:Bacterial Infections / Q000150:complications; D018736:DNA Adducts / Q000032:analysis*; D019175:DNA Methylation; D004534:Egypt; D004848:Epithelium / Q000737:chemistry*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D012553:Schistosomiasis haematobia / Q000150:complications; D001743:Urinary Bladder / Q000737:chemistry*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D018736:DNA Adducts; D006147:Guanine; C008450:7-methylguanine