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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Bladder tumor contains higher N7-methylguanine levels in DNA than adjacent normal bladder epithelium
Cancer Epidemiology Biomarkers and Prevention, Volume 15, No. 4, Year 2006
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Description
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. Copyright © 2006 American Association for Cancer Research.
Authors & Co-Authors
Saad, Abir Adel Abdel Razak
United Kingdom, Manchester
The Christie Nhs Foundation Trust
Egypt, Alexandria
Institute of Graduate Studies and Research
O'Connor, Peter J.
United Kingdom, Manchester
The Christie Nhs Foundation Trust
Mostafa, Mostafa Hassan
Egypt, Alexandria
Institute of Graduate Studies and Research
Metwalli, Nabila E.
Egypt, Alexandria
Alexandria University
Cooper, Donald P.
United Kingdom, Manchester
The Christie Nhs Foundation Trust
United Kingdom, Manchester
Gv Instruments Ltd
Margison, G. P.
United Kingdom, Manchester
The Christie Nhs Foundation Trust
Povey, Andrew C.
United Kingdom, Manchester
The Christie Nhs Foundation Trust
United Kingdom, Manchester
The University of Manchester
Statistics
Citations: 38
Authors: 7
Affiliations: 5
Identifiers
Doi:
10.1158/1055-9965.EPI-05-0813
ISSN:
10559965
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases