CYTOTOXICITY, CELLULAR ACCUMULATION AND DNA-BINDING OF OXALIPLATIN ISOMERS

被引:73
作者
PENDYALA, L
KIDANI, Y
PEREZ, R
WILKES, J
BERNACKI, RJ
CREAVEN, PJ
机构
[1] NAGOYA CITY UNIV,FUGISAWA,AICHI,JAPAN
[2] ROSWELL PK CANC INST,DEPT EXPTL THERAPEUT,BUFFALO,NY 14263
关键词
OXALIPLATIN; CYTOTOXICITY; ACCUMULATION; DNA BINDING;
D O I
10.1016/0304-3835(95)03974-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Oxaliplatin (trans-l-1,2-diaminocyclohexane oxalato Pt(II); 1R,2R-dach, l-OHP), its trans-d isomer (1S,2S-dach) and cis-dach (1R,2S-dach) isomers were compared in in vitro testing against human ovarian carcinoma cell lines A2780, A2780/CP (cisplatin resistant), A2780/l-OHP (oxaliplatin resistant), colon carcinoma cell line HT-29, and murine leukemia cell lines L1210, L1210/CP (cisplatin resistant), and L1210/dach (tetraplatin resistant). The relative molar potency of the three complexes in all the cell lines except:A2780/l-OHP and L1210/dach are trans-l > trans-d > cis-dach; in A2780/l-OHP they are trans-l = trans-d > cis-dach; in L1210/dach trans-l > trans-d = cis-dach. The A2780/l-OHP selected for trans-i resistance is 3.6-fold resistant to oxaliplatin, showed no resistance to trans-d isomer and is 6-fold resistant to cis-dach. However, L1210/dach which is selected for carboxyphthalato 1,2-dach (trans-dl) platinum(II) is 140-fold resistant to oxaliplatin, 73-fold resistant to trans-d, and 41-fold resistant to cis-OHP. The accumulation and DNA binding of platinum following a 2-h treatment of A2780 cells with each of the isomers (60 mu M) is in the order of trans-i > cis-dach > trans-d which corresponded to the cytotoxicity of trans-l, but not the others. The data suggest that other processes, such as differential formation of specific adducts and/or repair may be involved. Of the three isomers l-OHP is the superior and its accumulation and DNA binding are consistent with its cytotoxicity.
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页码:177 / 184
页数:8
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