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二甲基亚砜对顺二氨二氯铂在培养甲状腺细胞中诱导的毒性的调节作用。

Modulation by dimethyl sulphoxide of the toxicity induced by cis-diamminedichloroplatinum in cultured thyrocytes.

作者信息

Massart C, Le Tellier C, Gibassier J, Leclech G, Nicol M

机构信息

Service de Biochimie, CHU de Pontchaillou, 35033 Rennes, France.

出版信息

Toxicol In Vitro. 1993 Jan;7(1):87-94. doi: 10.1016/0887-2333(93)90116-m.

Abstract

Cis-diamminedichloroplatinum II (cisplatin) is an effective and widely used antitumour drug which induces many side-effects. We investigated the potency of dimethyl sulphoxide (DMSO) as an antidote to cisplatin-induced damage to cultured human thyrocytes. The effects of DMSO were studied on human thyroid cells cultured in monolayers and in follicles. Addition of 2% DMSO suppressed the cisplatin-induced decrease in intracellular lactate dehydrogenase, alpha-hydroxybutyryldehydrogenase and creatine kinase activities and in neutral red uptake. DMSO also partially or totally abolished the inhibition of cyclic AMP (cAMP), thyroglobulin (Tg) and triiodothyronine (T(3)) production observed with 7.5, 15 or 30 mum-cisplatin. In the presence of 75 mum-cisplatin, cAMP, Tg and T(3) secretion was always totally inhibited. The increase in thyroxine levels observed with cisplatin administration did not occur in the presence of DMSO. These data indicate that 2% DMSO interacted with cisplatin and therefore prevented the cytotoxic and inhibitory effects of cisplatin on cultured thyroid cells.

摘要

顺二氯二氨铂(顺铂)是一种有效且广泛使用的抗肿瘤药物,但会引发多种副作用。我们研究了二甲基亚砜(DMSO)作为顺铂诱导的培养人甲状腺细胞损伤解毒剂的效力。研究了DMSO对单层培养和滤泡培养的人甲状腺细胞的影响。添加2%的DMSO可抑制顺铂诱导的细胞内乳酸脱氢酶、α-羟丁酸脱氢酶和肌酸激酶活性以及中性红摄取的降低。DMSO还部分或完全消除了7.5、15或30 μmol顺铂对环磷酸腺苷(cAMP)、甲状腺球蛋白(Tg)和三碘甲状腺原氨酸(T3)产生的抑制作用。在75 μmol顺铂存在的情况下,cAMP、Tg和T3的分泌总是被完全抑制。在DMSO存在的情况下,顺铂给药后观察到的甲状腺素水平升高并未出现。这些数据表明,2%的DMSO与顺铂相互作用,因此防止了顺铂对培养甲状腺细胞的细胞毒性和抑制作用。

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