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 ill animal tests. Although the carcinog enicity is well established, the results of mutagenicity tests perform ed an 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 comp ounds were also tested by an Escherichia coli DNA repair-assay. The re sults of the repair tests indicate that unsymmetrically alkylated hydr azines can cause DNA-lesions which are lethal in repair-deficient stra ins. Finally QSAR (Quantitative Structure Activity Relationships) was used td develop La model to describe the genotoxic mechanism of hydraz ine compounds, taking advantage of the results of previous mutagenicit y studies. Energy of the lowest unoccupied molecular orbital together with. octanol-water partition coefficient explains nearly completely t he mutagenic activity of alkylated hydrazine compounds included in the analysis. The mutagenic activity of unsubstituted hydrazine is appare ntly based on different mechanisms.