Relative lack of toxicity of transplatin compared with cisplatin in rodents

The differential toxicity of the cis- and trans-isomers of diamminedichloroplatinum (II) (cisplatin and transplatin) was investigated in rats and guinea pigs. In both species, repeated daily administration of 1 to 2 mg per kg cisplatin produced severe histological and/or functional damage to renal and gastro-intestinal systems and resulted in death of the animals. Quantification of tissue platinum by atomic absorption spectroscopy demonstrated accumulation of large amounts of platinum in the kidney of the animals, with lesser amounts in the liver and gastro-intestinal tract. Transplatin, administered at total doses two- to four-fold that of cisplatin, was essentially non-toxic by histological and functional assessment. However, the amounts of tissue platinum measured in transplatin-treated animals were no smaller than those measured in cisplatin-treated animals; indeed, platinum concentrations in kidneys of transplatin-treated rats were more than 2.5 times those in cisplatin-treated rats. Thus tissue platinum content did not correlate with organ damage. These data suggest that mechanism(s) involving steric interactions of platinum species, perhaps with cellular macromolecules such as DNA or RNA, may be important in the differential toxicity of these two compounds.