Mutagenic activity of anticancer agent cis-dichlorodiammine platinum-II.
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.
D000818:Animals; D001853:Bone Marrow / Q000648:ultrastructure; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000648:ultrastructure; D051379:Mice; D009153:Mutagens; D012854:Sister Chromatid Exchange
D009153:Mutagens; D002945:Cisplatin