EFFECTS OF CISPLATIN AND ORG.2766 IN CHICK EMBRYONIC BRAIN-CELL CULTURES

被引:10
作者
BRUININK, A [1 ]
BIRCHLER, F [1 ]
机构
[1] UNIV ZURICH,CH-8603 SCHWERZENBACH,SWITZERLAND
关键词
CISPLATIN; ORG.2766; ACTH4-9; ANALOG; BRAIN; IN-VITRO;
D O I
10.1007/BF01973703
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The neurotoxicity of cisplatin and ORG.2766, both separately and in combination, was investigated using serum-free chick embryonic brain cell cultures. At low cisplatin concentrations glial cells were affected more than nerve cells. The onset of cisplatin toxicity was delayed, the major effects only being seen after the treatment was finished and when no free cisplatin was present in the culture medium. The data further indicate that the area under the graph of free cisplatin concentration in the culture medium against time (AUC) is a measure of cisplatin toxicity. The AUC of free cisplatin in the culture medium which causes a 50% reduction in the expression of glial fibrillary associated protein (GFAP) was similar to blood AUC values in humans known to induce neurotoxic effects in around 80% of patients. ORG.2766 at very high concentrations increased lysosomal activity, as measured by neutral red uptake, and the expression of GFAP. ORG.2766 did not influence the toxicity of cisplatin in culture.
引用
收藏
页码:325 / 329
页数:5
相关论文
共 28 条
[1]  
ANDREWS PA, 1988, CANCER RES, V48, P68
[2]   A PHASE-II STUDY OF CISPLATIN THERAPY IN RECURRENT CHILDHOOD BRAIN-TUMORS - A REPORT FROM THE CHILDRENS-CANCER-STUDY-GROUP [J].
BERTOLONE, SJ ;
BAUM, ES ;
KRIVIT, W ;
HAMMOND, GD .
JOURNAL OF NEURO-ONCOLOGY, 1989, 7 (01) :5-11
[3]   NEUROTROPHIC FACTORS AND REGENERATION IN THE PERIPHERAL NERVOUS-SYSTEM [J].
BIJLSMA, WA ;
JENNEKENS, FGI ;
SCHOTMAN, P ;
GISPEN, WH .
PSYCHONEUROENDOCRINOLOGY, 1984, 9 (03) :199-215
[4]   ONTOGENY OF MAP2 AND GFAP ANTIGENS IN PRIMARY CULTURES OF EMBRYONIC CHICK BRAIN - EFFECT OF SUBSTRATUM, OXYGEN-TENSION, SERUM AND ARA-C [J].
BRUININK, A ;
REISER, P .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 1991, 9 (03) :269-279
[5]  
Bruinink A., 1992, BRAIN BITS PIECES, P23
[6]   CISPLATIN METABOLITES IN PLASMA, A STUDY OF THEIR PHARMACOKINETICS AND IMPORTANCE IN THE NEPHROTOXIC AND ANTITUMOUR ACTIVITY OF CISPLATIN [J].
DALEYYATES, PT ;
MCBRIEN, DCH .
BIOCHEMICAL PHARMACOLOGY, 1984, 33 (19) :3063-3070
[7]   ELECTROPHYSIOLOGICAL STUDY OF THE PERIPHERAL AND CENTRAL NEUROTOXIC EFFECT OF CISPLATIN [J].
DAUGAARD, GK ;
PETRERA, J ;
TROJABORG, W .
ACTA NEUROLOGICA SCANDINAVICA, 1987, 76 (02) :86-93
[8]   ORG-2766 PROTECTS FROM CISPLATIN-INDUCED NEUROTOXICITY IN RATS [J].
DEKONING, P ;
NEIJT, JP ;
JENNEKENS, FGI ;
GISPEN, WH .
EXPERIMENTAL NEUROLOGY, 1987, 97 (03) :746-750
[9]  
EDWARDS PM, 1985, SENILE DEMENTIA ALZH, P231
[10]  
FAUCHON F, 1986, J NEURORADIOLOGY, V13, P151