Studies of induction of metallothionein in JAr (human choriocarcinoma) cells by cis and trans isomers of diamminedichloroplatinum (II) and their hydrolyzed species.
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.
Harford
C
C
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Sarkar
B
B
D001711:Biotransformation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000378:metabolism*; D002945:Cisplatin / Q000494:pharmacology*; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006868:Hydrolysis; D007536:Isomerism; D008668:Metallothionein / Q000032:analysis / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
C034697:transplatin; D008668:Metallothionein; D002945:Cisplatin