INVOLVEMENT OF HYDROXYL RADICAL FORMATION AND DNA STRAND BREAKAGE IN THE CYTOTOXICITY OF ANTHRAQUINONE ANTITUMOR AGENTS

被引:34
作者
FISHER, GR
BROWN, JR
PATTERSON, LH
机构
[1] CITY LEICESTER POLYTECH,DEPT PHARM,LEICESTER LE1 9BH,ENGLAND
[2] SUNDERLAND POLYTECH,DEPT PHARMACEUT SCI,SUNDERLAND SR2 7EE,DURHAM,ENGLAND
来源
FREE RADICAL RESEARCH COMMUNICATIONS | 1990年 / 11卷 / 1-3期
关键词
Anthraquinones; Cytotoxicity; DNA strand breaks; Hydroxyl radicals; MCF-7; cells;
D O I
10.3109/10715769009109674
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Four 9,10-anthraquinones (AQ) mono- or bis-substituted with the -NH(CH2)2 NH(CH2)2OH group were studied. 1-AQ, 1,5-AQ and 1,8-AQ but not 1,4-AQ (100°M) generated pBR322 plasmid DNA single strand breaks in the presence of purified NADPH dependent cytochrome P450 reductase. 1-AQ, 1,5-AQ and 1,8-AQ (at 100 °M) stimulated hydroxyl radical formation in MCF-7 S9 cell fraction (as measured by dimethyl pyrolline N-oxide spin trapping) and MCF-7 DNA strand breaks as measured by alkaline filter elution. In contrast 1,4-AQ did not stimulate hydroxyl radical formation and produced considerably less strand breaks in MCF-7 cells compared to the other AQ's. It would appear that the position of the -NH(CH2)2 NH(CH2)2OH groups on the chromophore is an important determinant in the metabolic activation of cytotoxic anthraquinones. This may contribute to the cytotoxicity (ID50 values) of 1-AQ (0.06 °M), 1-8-AQ (0.5 °M) and 1,5-AQ (12.3 °M) but not the 1,4-AQ (1.2 °M). © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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页码:117 / 125
页数:9
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