Metallothionein induction in mouse tissues by cis-dichlorodiammineplatinum(II) and its hydrolysis products

Chem Biol Interact. 1989;69(4):319-32. doi: 10.1016/0009-2797(89)90118-x.

Abstract

cis-Dichlorodiammineplatinum(II) (cis-DDP) doubled the amount of metallothioneins (MTs) in the livers and kidneys of BALB/c mice when injected i.p. in a single high dose of 30 mumol/kg (9 mg/kg). Two such doses given 17 h apart increased hepatic MTs 5-fold and also increased the relative rate of incorporation of radiolabelled cyst(e)ine into hepatic MTs. Hydrolysed cis-DDP was more effective than cis-DDP, increasing MT-bound zinc 27-fold and [3H]cysteine incorporation 6-fold in liver while doubling each of these in kidney. The MTs from the livers of mice treated with cis-DDP bound zinc, copper and platinum in ratios of 5:1:0.3, respectively, similar to those in whole liver and its soluble fraction, indicating that MTs do not selectively sequester platinum under these circumstances. The effects of cis-DDP on zinc and copper levels in serum, liver and kidney suggest that induction of MTs by cis-DDP is not mediated by displacement of endogenous zinc. Indirect induction by corticosteroids secreted in a stress response to cis-DDP is also an unlikely cause. cis-DDP, probably in a hydrolysed form, can therefore induce and bind to MTs in normal tissues, particularly when given at repeated high dosage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, Gel
  • Cisplatin / analogs & derivatives*
  • Cisplatin / pharmacology*
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Metallothionein / biosynthesis*
  • Metallothionein / isolation & purification
  • Mice
  • Mice, Inbred BALB C
  • Reference Values
  • Sulfates / pharmacology
  • Zinc / pharmacology
  • Zinc Sulfate

Substances

  • Sulfates
  • diamminediaqua platinum(II)
  • Zinc Sulfate
  • Metallothionein
  • Zinc
  • Cisplatin