EXPRESSION OF O(6)-ALKYLGUANINE-DNA-ALKYLTRANSFERASE INSITU IN OVARIAN AND HODGKINS TUMORS

被引:27
作者
LEE, SM [3 ]
HARRIS, M
RENNISON, J
MCGOWN, A
BROMLEY, M
ELDER, RH
RAFFERTY, JA
CROWTHER, D
MARGISON, GP
机构
[1] CRC,DEPT CARCINOGENESIS,OXFORD,ENGLAND
[2] PATERSON INST CANC RES,DEPT EXPTL PHARMACOL,MANCHESTER,ENGLAND
[3] CRC,DEPT MED ONCOL,OXFORD,ENGLAND
[4] CHRISTIE HOSP & HOLT RADIUM INST,DEPT PATHOL,MANCHESTER M20 9BX,LANCS,ENGLAND
关键词
D O I
10.1016/0959-8049(93)90079-U
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 atl 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.
引用
收藏
页码:1306 / 1312
页数:7
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