Genotoxic properties of the newly synthesized antineoplastic agents amidox, didox and trimidox.
Toxic and genotoxic effects of three polyhydroxy-substituted benzohydroxamates (amidox, didox and trimidox), having antineoplastic activities by the mechanism of the ribonucleotid reductase activity inhibition, were evaluated by reverse mutation assay on Salmonella typhimurium strains TA97, TA98, TA100, TA102. While amidox did not exhert any toxic effect, didox and trimidox were toxic. The toxicity of the test chemicals was dependent on the structure of their molecule and the repair capacity of the test strains. Trimidox exhibited the highest toxicity, and it was proved as a direct-acting frameshift mutagen. Its mutagenic effect was increased after a metabolic activation. Amidox and didox can be classified as frameshift promutagens.
Miadoková
E
E
Department of Genetics, Faculty of Sciences, Bratislava, Slovakia.
Macáková
K
K
Podstavková
S
S
Vlcek
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001550:Benzamidines / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D016368:Frameshift Mutation / Q000187:drug effects; D006877:Hydroxamic Acids / Q000633:toxicity*; D066298:In Vitro Techniques; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010091:Oximes / Q000633:toxicity*; D051381:Rats; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
C074761:3,4,5-trihydroxybenzamidoxime; D000970:Antineoplastic Agents; D001550:Benzamidines; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D009153:Mutagens; D010091:Oximes; C070491:Amidox; D012264:Ribonucleotide Reductases; C035419:3,4-dihydroxybenzohydroxamic acid