Inter- and intracellular heterogeneity of O-6-alkylguanine-DNA alkyltransferase expression in human brain tumours: Possible significance in nitrosourea therapy

被引:25
作者
Lee, SM
Reid, H
Elder, RH
Thatcher, N
Margison, GP
机构
[1] CHRISTIE HOSP NATL HLTH SERV TRUST,CRC,DEPT CARCINOGENESIS,PATERSON INST CANC RES,MANCHESTER M20 4BX,LANCS,ENGLAND
[2] UNIV MANCHESTER,SCH MED,DEPT PATHOL SCI,MANCHESTER M13 9PT,LANCS,ENGLAND
关键词
D O I
10.1093/carcin/17.4.637
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The inter- and intracellular distribution of the DNA repair protein O-6-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 similar to 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.
引用
收藏
页码:637 / 641
页数:5
相关论文
共 46 条
[1]  
AIDA T, 1987, CANCER RES, V47, P1361
[2]   INHIBITION OF O-6-ALKYLGUANINE-DNA-ALKYLTRANSFERASE ACTIVITY POTENTIATES CYTOTOXICITY AND INDUCTION OF SCES IN HUMAN GLIOMA-CELLS RESISTANT TO 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA [J].
AIDA, T ;
CHEITLIN, RA ;
BODELL, WJ .
CARCINOGENESIS, 1987, 8 (09) :1219-1223
[3]   INCREASED REPAIR OF O6-ALKYLGUANINE DNA ADDUCTS IN GLIOMA-DERIVED HUMAN-CELLS RESISTANT TO THE CYTOTOXIC AND CYTOGENETIC EFFECTS OF 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA [J].
BODELL, WJ ;
AIDA, T ;
BERGER, MS ;
ROSENBLUM, ML .
CARCINOGENESIS, 1986, 7 (06) :879-883
[4]  
CHANG CH, 1983, CANCER, V52, P997, DOI 10.1002/1097-0142(19830915)52:6<997::AID-CNCR2820520612>3.0.CO
[5]  
2-2
[6]  
CITRON M, 1991, CANCER RES, V51, P4131
[7]  
DAY RS, 1983, P AM ASSOC CANC RES, V24, P335
[8]   IMPORTANCE OF THE DNA-REPAIR ENZYME O-6-ALKYL GUANINE ALKYLTRANSFERASE (AT) IN CANCER-CHEMOTHERAPY [J].
DINCALCI, M ;
CITTI, L ;
TAVERNA, P ;
CATAPANO, CV .
CANCER TREATMENT REVIEWS, 1988, 15 (04) :279-292
[9]   EXPRESSION OF MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE IN A CELL-LINE SENSITIVE TO ALKYLATING-AGENTS [J].
DOLAN, ME ;
NORBECK, L ;
CLYDE, C ;
HORA, NK ;
ERICKSON, LC ;
PEGG, AE .
CARCINOGENESIS, 1989, 10 (09) :1613-1619
[10]  
DOLAN ME, 1991, CANCER RES, V51, P3367