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

2.50
Hdl Handle:
http://hdl.handle.net/10541/72743
Title:
Bladder tumor contains higher N7-methylguanine levels in DNA than adjacent normal bladder epithelium.
Authors:
Saad, Abir A; O'Connor, Peter J; Mostafa, Mostafa H; Metwalli, Nabila E; Cooper, Donald P; Margison, Geoffrey P; Povey, Andrew C
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.
Affiliation:
Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester.
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
Issue Date:
Apr-2006
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
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorSaad, Abir A-
dc.contributor.authorO'Connor, Peter J-
dc.contributor.authorMostafa, Mostafa H-
dc.contributor.authorMetwalli, Nabila E-
dc.contributor.authorCooper, Donald P-
dc.contributor.authorMargison, Geoffrey P-
dc.contributor.authorPovey, Andrew C-
dc.date.accessioned2009-07-07T11:54:09Z-
dc.date.available2009-07-07T11:54:09Z-
dc.date.issued2006-04-
dc.identifier.citationBladder tumor contains higher N7-methylguanine levels in DNA than adjacent normal bladder epithelium. 2006, 15 (4):740-3 Cancer Epidemiol. Biomarkers Prev.en
dc.identifier.issn1055-9965-
dc.identifier.pmid16614117-
dc.identifier.doi10.1158/1055-9965.EPI-05-0813-
dc.identifier.urihttp://hdl.handle.net/10541/72743-
dc.description.abstractSchistosoma 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.en
dc.language.isoenen
dc.subjectUrinary Bladder Canceren
dc.subject.meshBacterial Infections-
dc.subject.meshDNA Adducts-
dc.subject.meshDNA Methylation-
dc.subject.meshEgypt-
dc.subject.meshEpithelium-
dc.subject.meshFemale-
dc.subject.meshGuanine-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshSchistosomiasis haematobia-
dc.subject.meshUrinary Bladder-
dc.subject.meshUrinary Bladder Neoplasms-
dc.titleBladder tumor contains higher N7-methylguanine levels in DNA than adjacent normal bladder epithelium.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester.en
dc.identifier.journalCancer Epidemiology, Biomarkers & Preventionen
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