Expression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours.
Authors
Lee, Siow MingHarris, Martin
Rennison, John
McGown, Alan T
Bromley, Michael
Elder, Rhoderick H
Rafferty, Joseph A
Crowther, Derek
Margison, Geoffrey P
Affiliation
CRC Department of Medical Oncology, Christie Hospital (NHS) Trust, Manchester, U.K.Issue Date
1993
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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.Citation
Expression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours. 1993, 29A (9):1306-12 Eur. J. CancerJournal
European Journal of CancerDOI
10.1016/0959-8049(93)90079-UPubMed ID
8343274Type
ArticleLanguage
enISSN
0959-8049ae974a485f413a2113503eed53cd6c53
10.1016/0959-8049(93)90079-U
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