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    Bladder tumor contains higher N7-methylguanine levels in DNA than adjacent normal bladder epithelium.

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    Authors
    Saad, Abir A
    O'Connor, Peter J
    Mostafa, Mostafa H
    Metwalli, Nabila E
    Cooper, Donald P
    Margison, Geoffrey P
    Povey, Andrew C
    Affiliation
    Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester.
    Issue Date
    2006-04
    
    Metadata
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    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 (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.
    Citation
    Bladder tumor contains higher N7-methylguanine levels in DNA than adjacent normal bladder epithelium. 2006, 15 (4):740-3 Cancer Epidemiol. Biomarkers Prev.
    Journal
    Cancer Epidemiology, Biomarkers & Prevention
    URI
    http://hdl.handle.net/10541/72743
    DOI
    10.1158/1055-9965.EPI-05-0813
    PubMed ID
    16614117
    Type
    Article
    Language
    en
    ISSN
    1055-9965
    ae974a485f413a2113503eed53cd6c53
    10.1158/1055-9965.EPI-05-0813
    Scopus Count
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    All Paterson Institute for Cancer Research

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