An empirical and theoretical study on mechanisms of mutagenic activity of hydrazine compounds.
Hydrazine compounds are important industrial and laboratory chemicals. Many of them are carcinogenic in animal tests. Although the carcinogenicity is well established, the results of mutagenicity tests performed on alkylhydrazines vary greatly in different studies. In an attempt to clarify the situation we have applied Salmonella typhimurium TA102 tests to hydrazine and its mono- and dimethyl derivatives. These compounds were also tested by an Escherichia coli DNA repair-assay. The results of the repair tests indicate that unsymmetrically alkylated hydrazines can cause DNA-lesions which are lethal in repair-deficient strains. Finally QSAR (Quantitative Structure Activity Relationships) was used to develop a model to describe the genotoxic mechanism of hydrazine compounds, taking advantage of the results of previous mutagenicity studies. Energy of the lowest unoccupied molecular orbital together with octanol-water partition coefficient explains nearly completely the mutagenic activity of alkylated hydrazine compounds included in the analysis. The mutagenic activity of unsubstituted hydrazine is apparently based on different mechanisms.
Poso
A
A
Department of Pharmaceutical Chemistry, University of Kuopio, Finland.
von Wright
A
A
Gynther
J
J
D004249:DNA Damage; D004269:DNA, Bacterial / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D006834:Hydrazines / Q000633:toxicity*; D008954:Models, Biological; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics
D004269:DNA, Bacterial; D006834:Hydrazines; D009153:Mutagens; C029424:hydrazine