Expression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours.

2.50
Hdl Handle:
http://hdl.handle.net/10541/99618
Title:
Expression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours.
Authors:
Lee, Siow Ming; Harris, Martin; Rennison, John; McGown, Alan T; Bromley, Michael; Elder, Rhoderick H; Rafferty, Joseph A; Crowther, Derek; Margison, Geoffrey P
Abstract:
The cellular expression of O6-alkylguanine-DNA-alkyltransferase (ATase) may be an important factor in determining tumour sensitivity to certain alkylating agents. In a comparative study, we have examined the inter- and intracellular distribution of ATase in tumour biopsies of a series of patients with Hodgkin's disease and ovarian cancer using a rabbit antihuman ATase antiserum. The antibody recognises the ATase protein on western blots of cell-free extracts of a number of ovarian tumours with ATase activities varying from 20 to 420 fmol/mg protein as determined by in vitro assay and there was a linear correlation between ATase activity and the intensity of the band on western blots (r = 0.993). Immunohistochemical staining was seen in all of the ovarian tumours examined and was confined to the nucleus. This is in contrast to the Hodgkin's tissue, where staining was much reduced and present in both nuclei and cytoplasm. The results suggest that in ovarian tumours the general resistance to nitrosourea chemotherapy may be related to the high cellular expression of ATase protein: this is in contrast to the more chemosensitive Hodgkin's disease. This raises the possibility that it might be feasible to predict sensitivity or resistance to these alkylating agents by immunohistochemical staining of tumour or tissue specimens.
Affiliation:
CRC Department of Medical Oncology, Christie Hospital (NHS) Trust, Manchester, U.K.
Citation:
Expression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours. 1993, 29A (9):1306-12 Eur. J. Cancer
Journal:
European Journal of Cancer
Issue Date:
1993
URI:
http://hdl.handle.net/10541/99618
DOI:
10.1016/0959-8049(93)90079-U
PubMed ID:
8343274
Type:
Article
Language:
en
ISSN:
0959-8049
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorLee, Siow Mingen
dc.contributor.authorHarris, Martinen
dc.contributor.authorRennison, Johnen
dc.contributor.authorMcGown, Alan Ten
dc.contributor.authorBromley, Michaelen
dc.contributor.authorElder, Rhoderick Hen
dc.contributor.authorRafferty, Joseph Aen
dc.contributor.authorCrowther, Dereken
dc.contributor.authorMargison, Geoffrey Pen
dc.date.accessioned2010-05-21T15:00:29Z-
dc.date.available2010-05-21T15:00:29Z-
dc.date.issued1993-
dc.identifier.citationExpression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours. 1993, 29A (9):1306-12 Eur. J. Canceren
dc.identifier.issn0959-8049-
dc.identifier.pmid8343274-
dc.identifier.doi10.1016/0959-8049(93)90079-U-
dc.identifier.urihttp://hdl.handle.net/10541/99618-
dc.description.abstractThe cellular expression of O6-alkylguanine-DNA-alkyltransferase (ATase) may be an important factor in determining tumour sensitivity to certain alkylating agents. In a comparative study, we have examined the inter- and intracellular distribution of ATase in tumour biopsies of a series of patients with Hodgkin's disease and ovarian cancer using a rabbit antihuman ATase antiserum. The antibody recognises the ATase protein on western blots of cell-free extracts of a number of ovarian tumours with ATase activities varying from 20 to 420 fmol/mg protein as determined by in vitro assay and there was a linear correlation between ATase activity and the intensity of the band on western blots (r = 0.993). Immunohistochemical staining was seen in all of the ovarian tumours examined and was confined to the nucleus. This is in contrast to the Hodgkin's tissue, where staining was much reduced and present in both nuclei and cytoplasm. The results suggest that in ovarian tumours the general resistance to nitrosourea chemotherapy may be related to the high cellular expression of ATase protein: this is in contrast to the more chemosensitive Hodgkin's disease. This raises the possibility that it might be feasible to predict sensitivity or resistance to these alkylating agents by immunohistochemical staining of tumour or tissue specimens.en
dc.language.isoenen
dc.subjectOvarian Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshBlotting, Western-
dc.subject.meshCystadenocarcinoma-
dc.subject.meshDrug Resistance-
dc.subject.meshFemale-
dc.subject.meshHodgkin Disease-
dc.subject.meshHumans-
dc.subject.meshImmune Sera-
dc.subject.meshImmunoenzyme Techniques-
dc.subject.meshMethyltransferases-
dc.subject.meshMiddle Aged-
dc.subject.meshO(6)-Methylguanine-DNA Methyltransferase-
dc.subject.meshOvarian Neoplasms-
dc.titleExpression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology, Christie Hospital (NHS) Trust, Manchester, U.K.en
dc.identifier.journalEuropean Journal of Canceren
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