THE TOXICITY OF ORGANOPHOSPHATE COMPOUNDS TOWARDS CULTURED PC12 CELLS

被引:34
作者
FLASKOS, J
MCLEAN, WG
HARGREAVES, AJ
机构
[1] ARISTOTELIAN UNIV THESSALONIKI,FAC VET MED,BIOCHEM & TOXICOL LAB,THESSALONIKI,GREECE
[2] UNIV LIVERPOOL,DEPT PHARMACOL & THERAPEUT,LIVERPOOL L69 3BX,ENGLAND
基金
英国惠康基金;
关键词
ORGANOPHOSPHATES; PC12; CELLS; ANTIPROLIFERATIVE ACTIVITY; CYTOTOXICITY;
D O I
10.1016/0378-4274(94)90146-5
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
The effects of three representative organophosphates (OPs), tricresyl phosphate (TCP), triphenyl phosphite (TPP) and paraoxon (POX) on the proliferation and viability of rat PC12 pheochromocytoma cells were studied. With respect to its IC50, TCP was at least an order of magnitude more potent in its antiproliferative activity than both TPP and POX. All test OPs were cytotoxic at concentrations inhibiting cell proliferation. No compound inhibited cell growth below 10 mu g/ml. For TCP and TPP the estimated IC50 values from proliferation assays were lower than published LD(50) values in vivo, whereas paraoxon was much less toxic in vitro than in vivo. Subcytotoxic levels of TCP (1 mu g/ml) were found to inhibit the maintenance of neurites on cells grown in the presence of nerve growth factor.
引用
收藏
页码:71 / 76
页数:6
相关论文
共 16 条
[1]   CYTOSKELETAL PROTEINS AS TARGETS FOR ORGANO-PHOSPHORUS COMPOUND AND ALIPHATIC HEXACARBON-INDUCED NEUROTOXICITY [J].
ABOUDONIA, MB ;
LAPADULA, DM ;
SUWITA, E .
TOXICOLOGY, 1988, 49 (2-3) :469-477
[2]  
ABOUDONIA MB, 1990, ANNU REV PHARMACOL, V30, P405, DOI 10.1146/annurev.pa.30.040190.002201
[3]  
BHUYAN BK, 1976, EXP CELL RES, V97, P274
[4]   EFFECTS OF CERTAIN METABOLICALLY ACTIVE DRUGS AND OXIMES ON TRI-O-CRESYL PHOSPHATE TOXICITY [J].
BLEIBERG, MJ ;
JOHNSON, H .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1965, 7 (02) :227-&
[5]  
DUSTIN P, 1984, MICROTUBULES
[6]   REGULATION OF THE DIFFERENTIATION OF PC12 PHEOCHROMOCYTOMA CELLS [J].
FUJITA, K ;
LAZAROVICI, P ;
GUROFF, G .
ENVIRONMENTAL HEALTH PERSPECTIVES, 1989, 80 :127-142
[7]   SYNTHESIS, STORAGE AND RELEASE OF ACETYLCHOLINE BY A NORADRENERGIC PHEOCHROMOCYTOMA CELL LINE [J].
GREENE, LA ;
REIN, G .
NATURE, 1977, 268 (5618) :349-351
[8]  
HATCH RC, 1988, VET PHARM THERAPEUTI, P1053
[9]   ORGANOPHOSPHATES AND DELAYED NEUROPATHY - IS NTE ALIVE AND WELL [J].
JOHNSON, MK .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1990, 102 (03) :385-399
[10]   ORGANOPHOSPHORUS ESTERS CAUSING DELAYED NEUROTOXIC EFFECTS - MECHANISM OF ACTION AND STRUCTURE-ACTIVITY STUDIES [J].
JOHNSON, MK .
ARCHIVES OF TOXICOLOGY, 1975, 34 (04) :259-288