Expression of O6-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients

摘要

Bladder tumour tissues and corresponding uninvolved mucosa (normal tissue) of Egyptian bladder cancer patients were assessed for O⁶-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/μg 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 (P < .01) 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% P = .04) and (1.89 ± 1.42; P < .01), respectively. These observationssuggest that, overall, MGMT levels are increased during humanbladder carcinogenesis and that MGMT downregulation is not acommon feature of bladder cancers. Based on this, bladder cancerswould be expected to be relatively resistant to chemotherapy whichinvolved O⁶-guanine alkylating antitumour agents.