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Promutagenic methylation damage in bladder DNA from patients with bladder cancer associated with schistosomiasis and from normal individuals
1institute for Graduate Studies and Research
2Faculty of Medicine, University of Alexandria Horreya Avenue, Alexandria, Egypt
3Department of Histopathology, Withington Hospital Manchester M20 8LR
4CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute Manchester M20 9BX, UK
5To whom correspondence should be addressed
Radioimmunoassays (RIAs) have been used to detect the promutagenk lesion O6-methyldeoxyguanosine (O6-MedG) in DNA isolated from the bladder tissues of Egyptian patients presenting with bladder carcinoma and concomitant schistosomiasis (bilharziasis), a parasitic disease known to be associated with the presence of N-nitrosamines in the urine. Alkylation damage was present in the DNA of the majority of the samples (44/46, 96%); 38 samples were of tumour tissue and 8 from uninvolved bladder mucosa. Levels of O6-MedG ranged from undetectable (ND; i.e. <0.01 µmol O6-MedG/mol dG) to 0.485 µmol/mol dG with an overall mean of 0.134 ± 0.10 µmol/mol dG, including the two samples that were below the limit of detection. In contrast, methylation damage was detected in only 4/12 (33%) of the DNA samples from normal bladder tissue of European origin. In these samples levels of O6-MedG ranged from ND to 0.225 µmol/mol dG with an overall mean of 0.046 ± 0.082 µmol O6-MedG/mol dG. These results confirm that alkylation events can be detected in the DNA of schistosome-infected human bladder tissue. The methylation of uninvolved and tumour tissue DNA to similar extents suggests that the alkylating intermediate may have been present in the urine. These results indicate the need for further investigation to determine whether relationships exist between levels of DNA damage and the prevalence of schistosome infection and/or the extent and type of bacterial infection that frequently accompanies this disease.
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