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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| Format: | Article |
| Language: | English |
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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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| author | Abir A. Saad Heba Sh. Kassem Andrew C. Povey Geoffrey P. Margison |
| author_facet | Abir A. Saad Heba Sh. Kassem Andrew C. Povey Geoffrey P. Margison |
| author_sort | Abir A. Saad |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-4f9058ef1d8c493d8e366f3a812728a9 |
| institution | Kabale University |
| issn | 2090-021X |
| language | English |
| publishDate | 2010-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Nucleic Acids |
| spelling | doaj-art-4f9058ef1d8c493d8e366f3a812728a92025-02-03T05:58:45ZengWileyJournal of Nucleic Acids2090-021X2010-01-01201010.4061/2010/840230840230Expression of O6-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian PatientsAbir A. Saad0Heba Sh. Kassem1Andrew C. Povey2Geoffrey P. Margison3Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, The University of Manchester, Manchester M20 4BX, UKCancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, The University of Manchester, Manchester M20 4BX, UKCentre for Occupational and Environmental Health, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PL, UKCancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, The University of Manchester, Manchester M20 4BX, UKBladder 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.http://dx.doi.org/10.4061/2010/840230 |
| spellingShingle | Abir A. Saad Heba Sh. Kassem Andrew C. Povey Geoffrey P. Margison Expression of O6-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients Journal of Nucleic Acids |
| title | Expression of O6-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients |
| title_full | Expression of O6-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients |
| title_fullStr | Expression of O6-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients |
| title_full_unstemmed | Expression of O6-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients |
| title_short | Expression of O6-Alkylguanine-DNA Alkyltransferase in Normal and Malignant Bladder Tissue of Egyptian Patients |
| title_sort | expression of o6 alkylguanine dna alkyltransferase in normal and malignant bladder tissue of egyptian patients |
| url | http://dx.doi.org/10.4061/2010/840230 |
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