Expression of O6-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients
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...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2010-01-01
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| Series: | Journal of Nucleic Acids |
| Online Access: | http://dx.doi.org/10.4061/2010/840230 |
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| Summary: | 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 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 O6-guanine alkylating antitumour agents. |
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| ISSN: | 2090-021X |