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Journal of Nucleic Acids
Volume 2010 (2010), Article ID 840230, 9 pages
http://dx.doi.org/10.4061/2010/840230
Research Article

Expression of -Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients

1Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, The University of Manchester, Manchester M20 4BX, UK
2Institute of Graduate Studies and Research, University of Alexandria, Alexandria 21526, Egypt
3Pathology Department and Clinical Genomics Center, Faculty of Medicine, University of Alexandria, Alexandria 21526, Egypt
4Centre for Occupational and Environmental Health, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PL, UK

Received 12 June 2010; Accepted 17 August 2010

Academic Editor: Ashis Basu

Copyright © 2010 Abir A. Saad et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Bladder tumour tissues and corresponding uninvolved mucosa (normal tissue) of Egyptian bladder cancer patients were assessed for -alkylguanine-DNA-alkyltransferase (MGMT) activity by functional assay of tissue extracts (36 paired samples), and distribution by immunofluorescence (IF) microscopy of fixed material (24 paired samples). MGMT varied widely from 42–253 fmoles/mg protein and from 3.2–40 fmoles/ g DNA in normal and 58–468 fmoles/mg protein and 2.5–49.5 fmoles/mg protein, in the tumour tissues; only one tumour had undetectable activity. Pairwise comparison of MGMT activity in tumour and adjacent normal tissue showed no significant difference based on DNA content but was 1.75-fold higher in tumour ( ) based on protein. There was no effect of gender or bilharzia infection status. IF showed that in tumours, both the mean percentage of positive nuclei (57.3 20.3%) and mean integrated IF (5.47 3.66) were significantly higher than those in uninvolved tissues (42.8 13.5% ) and (1.89 1.42; ), respectively. These observations suggest that, overall, MGMT levels are increased during human bladder carcinogenesis and that MGMT downregulation is not a common feature of bladder cancers. Based on this, bladder cancers would be expected to be relatively resistant to chemotherapy which involved -guanine alkylating antitumour agents.