Interaction of cis- and trans-diamminedichloroplatinum with metallothionein in vivo.

The properties of platinum (II) complexes to induce the biosynthesis of metallothionein (MT) were investigated in rabbits following injections of K2PtCl4, cis and trans isomers of DDP (diammine-dichloroplatinum). It was demonstrated that cis-DDP has an ability to induce MT specifically in the liver, whereas trans-DDP appears to be unable to stimulate the biosynthesis of MT in either the liver or the kidneys. In contrast, K2PtCl4 is effective to elevate the MT level in both tissues. However, all of these platinum complexes are rather poor stimulators for MT biosynthesis compared to cadmium and zinc compounds. Preinjection with Zn(NO3)2 significantly enhances the amount of Pt associated with the MT fractions compared to that resulting from injections with either cis- or trans-DDP without Zn(NO3)2 pretreatment. Metallothionein containing Pt was purified and identified from the liver and kidneys of rabbits after preinjections with Zn(NO3)2 followed by repeated injections of cis-DDP and trans-DDP, respectively. It was found for the first time that a relatively higher degree of Pt was associated with MT fractions in the case of trans-DDP treatment than that of cis-DDP injection. On this basis, the role of MT was discussed in relation to its involvement in the metabolism of cis-DDP, and the difference of the antitumor activity and toxicity between cis- and trans-DDP.