Studies of induction of metallothionein in JAr (human choriocarcinoma) cells by cis and trans isomers of diamminedichloroplatinum (II) and their hydrolyzed species.

Molecular toxicology Pub Date : 1989-04-01
C Harford, B Sarkar
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Abstract

The inducibility of metallothionein by cis- and trans-diamminedichloroplatinum(II) and their hydrolyzed products was studied in the JAr (a human choriocarcinoma) cell line. The metallothionein present in the cytosolic fraction of these cells was measured after a 12- or 24-h exposure to a fresh metal solution or a solution that had been allowed to hydrolyze. These results demonstrate that hydrolysis of the cis isomer produces a species that is able to give a 374% increase in the cytosolic level of metallothionein after a 24-h exposure to 40 microM of the metal. Fresh cisplatin, on the other hand, gives a maximal increase of 118% under the same conditions. Transplatin and its hydrolyzed species did not induce metallothionein. These results may indicate that hydrolysis of cisplatin performs an important role in the metabolism and possibly the toxicity of this widely used agent for cancer chemotherapy.

二胺二氯铂(II)顺、反式异构体及其水解产物对人绒毛膜癌细胞金属硫蛋白诱导作用的研究。
在人绒毛膜癌细胞株JAr中研究了顺式和反式二胺氯化铂及其水解产物对金属硫蛋白的诱导作用。在新鲜金属溶液或已被允许水解的溶液中暴露12或24小时后,测量这些细胞细胞质部分中存在的金属硫蛋白。这些结果表明,顺式异构体的水解产生一种在暴露于40微米金属24小时后能够使细胞内金属硫蛋白水平增加374%的物种。另一方面,在相同条件下,新鲜顺铂的最大增幅为118%。移植及其水解产物不诱导金属硫蛋白。这些结果可能表明顺铂的水解在这种广泛用于癌症化疗的药物的代谢和可能的毒性中起着重要作用。
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