Mutagenic activity of anticancer agent cis-dichlorodiammine platinum-II

Mutat Res. 1979 Sep;68(1):69-77. doi: 10.1016/0165-1218(79)90079-x.

Abstract

cis-Dichlorodiamminoplatinum-II (cis-DDP) has been widely used as an anticancer chemotherapeutic agent. The mutagenicity of cis-DDP was investigated in vitro and in vivo using sister-chromatid exchange analysis and the analysis of chromosomal aberrations. Parallel human lymphocyte cultures were incubated with and without the addition of BrdU at 4 concentrations of cis-DDP. Significant increases in SCE rate were observed at 0.25 micrograms/ml and higher, showing a clear dose-response relation between SCE rate and cis-DDP concentration. A significant increase in chromosome breakage and tetraradial figures was observed in BrdU free cultures treated with cis-DDP again showing a dose dependency. Analysis of the distribution of cells in the first, second and third division in cis-DDP treated cultures demonstrated the depressing effect of the drug on mitotic activity. In vivo analysis of SCE and chromosome aberrations in mouse showed that 13.85 mg/kg i.p. of cis-DDP produces significant increases in the rate of SCE and chromosome aberrations in bone-marrow cells.

MeSH terms

  • Animals
  • Bone Marrow / ultrastructure
  • Cells, Cultured
  • Chromosome Aberrations
  • Chromosomes / drug effects*
  • Cisplatin / pharmacology*
  • Humans
  • Lymphocytes / ultrastructure
  • Mice
  • Mutagens*
  • Sister Chromatid Exchange

Substances

  • Mutagens
  • Cisplatin