Inter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumors: possible significance in nitrosourea therapy.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95697
Title:
Inter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumors: possible significance in nitrosourea therapy.
Authors:
Lee, Siow Ming; Reid, H; Elder, Rhoderick H; Thatcher, Nick; Margison, Geoffrey P
Abstract:
The inter- and intracellular distribution of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase) may be an important factor in the sensitivity or resistance of tumours to treatment with certain alkylating agents, including the methyltriazenes and nitrosoureas. In order to examine this issue 26 human brain tumour sections (23 high grade gliomas and three low grade gliomas) were examined for ATase expression by immunohistochemistry using a rabbit anti-human ATase polyclonal antibody. Positive staining, seen as fine black granules mainly confined to the nucleus, was observed in all the glioma sections examined. There was marked cellular heterogeneity, ranging from cells completely devoid of staining to cells with very intense staining. Semi-quantitatively, in the 23 high grade gliomas examined six had 1+ staining, seven had 2+ staining and 10 had 3+ staining, whereas all three low grade gliomas had 1+ staining. These results are in contrast to published reports showing that approximately 35% of human brain tumour-derived cell lines and xenografts had very low levels of ATase activity and suggest that the complete lack of ATase is not a common occurrence in high grade glioma.
Affiliation:
CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Manchester, UK.
Citation:
Inter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumors: possible significance in nitrosourea therapy. 1996, 17 (4):637-41 Carcinogenesis
Journal:
Carcinogenesis
Issue Date:
Apr-1996
URI:
http://hdl.handle.net/10541/95697
DOI:
10.1093/carcin/17.4.637
PubMed ID:
8625471
Type:
Article
Language:
en
ISSN:
0143-3334
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLee, Siow Mingen
dc.contributor.authorReid, Hen
dc.contributor.authorElder, Rhoderick Hen
dc.contributor.authorThatcher, Nicken
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2010-04-06T11:16:34Z-
dc.date.available2010-04-06T11:16:34Z-
dc.date.issued1996-04-
dc.identifier.citationInter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumors: possible significance in nitrosourea therapy. 1996, 17 (4):637-41 Carcinogenesisen
dc.identifier.issn0143-3334-
dc.identifier.pmid8625471-
dc.identifier.doi10.1093/carcin/17.4.637-
dc.identifier.urihttp://hdl.handle.net/10541/95697-
dc.description.abstractThe inter- and intracellular distribution of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase) may be an important factor in the sensitivity or resistance of tumours to treatment with certain alkylating agents, including the methyltriazenes and nitrosoureas. In order to examine this issue 26 human brain tumour sections (23 high grade gliomas and three low grade gliomas) were examined for ATase expression by immunohistochemistry using a rabbit anti-human ATase polyclonal antibody. Positive staining, seen as fine black granules mainly confined to the nucleus, was observed in all the glioma sections examined. There was marked cellular heterogeneity, ranging from cells completely devoid of staining to cells with very intense staining. Semi-quantitatively, in the 23 high grade gliomas examined six had 1+ staining, seven had 2+ staining and 10 had 3+ staining, whereas all three low grade gliomas had 1+ staining. These results are in contrast to published reports showing that approximately 35% of human brain tumour-derived cell lines and xenografts had very low levels of ATase activity and suggest that the complete lack of ATase is not a common occurrence in high grade glioma.en
dc.language.isoenen
dc.subjectBrain Canceren
dc.subject.meshAntineoplastic Agents, Alkylating-
dc.subject.meshAstrocytoma-
dc.subject.meshBlotting, Western-
dc.subject.meshBrain Neoplasms-
dc.subject.meshCarmustine-
dc.subject.meshGlioblastoma-
dc.subject.meshHumans-
dc.subject.meshImmunohistochemistry-
dc.subject.meshMethyltransferases-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.titleInter- and intracellular heterogeneity of O6-alkylguanine-DNA alkyltransferase expression in human brain tumors: possible significance in nitrosourea therapy.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalCarcinogenesisen

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