Investigations on mutagenicity and genotoxicity of pentamidine and some related trypanocidal diamidines.
Pentamidine, DAPI and some related compounds (DAI, 6-Br-AI, DPTN, DIPI, 3-Am-DAI, DiaPBF) were investigated in 2 different screening test systems for their potential mutagenic and cytotoxic effects, in the light of their binding to DNA. In the Ames test using Salmonella typhimurium strains TA98 and TA100 with and without metabolic activation no mutagenic effects could be observed. All diamidines tested, except DAI, were toxic at concentrations of 0.5 and 1.0 mumole/plate. In the sister-chromatid exchange (SCE) assay with human peripheral lymphocytes all compounds tested were growth-retarding particularly in the G0 phase. A significant induction of SCEs could only be seen after treatment with the monoamidino compound 6-Br-AI at a concentration of 100 mumole/l. It is concluded from the data obtained that pentamidine and related diamidines in the 2 assays tested show no mutagenic or genotoxic effects, in spite of their tight binding to DNA.
Stauffert
I
I
Institut für Pharmacokologie und Toxikologie, Universität Erlangen-Nürnberg, F.R.G.
Paulini
H
H
Steinmann
U
U
Sippel
H
H
Estler
C J
CJ
D000578:Amidines / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D009152:Mutagenicity Tests; D009153:Mutagens; D010419:Pentamidine / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000494:pharmacology*
D000578:Amidines; D007211:Indoles; D009153:Mutagens; D014344:Trypanocidal Agents; C007293:DAPI; D010419:Pentamidine