Experimental study of the mechanisms of toxic action of unsymmetrical dimethylhydrazine in chronic administration cological

The purpose of this work was to study the mechanisms of toxic action of unsymmetrical dimethylhydrazine (UDMH). The evaluation of genotoxic and cytotoxic effects; the study of contribution of oxidative action of UDMH to nuclear DNA in chronic administration to white rats for 7; 14; and 21 days at a dose of 10 and 20 mg/kg as well as pathomorphological studies have been performed.

The unsymmetrical dimethylhydrazine used for the experiments contained 97;26% of 1;1-dimethylhydrazine and 0;07% of N-nitrosodimethylamine.

The genotoxic and cytotoxic effects of UDMH were determined using alkaline gel electrophoresis (DNA comet assay) on leukocytes; hepatocytes; and cortical cells. It has been shown that a three-week administration of UDMH at doses of 10 and 20 mg/kg did not cause significant genotoxic and cytotoxic effect on nuclear DNA in the studied cells.

The pathomorphological study of the toxic effect of UDMH revealed moderate changes in the conducting pathways (rarefaction of the neuropil) in the brain. Full blood and single foci of necrosis of hepatocytes have been found in the liver. A slight increase in the frequency of occurrence of single foci of hepatocyte necrosis with the increase in the duration of UDMH administration has been noted.

After determining the oxidative effect of UDMH on the nuclear DNA of leukocytes; hepatocytes; and brain cells using formamidopyrimidine glycosylase DNA comet assay; an increase in the content of reactive oxygen species in hepatocytes has been found after administration of UDMH at a dose of 20 mg/kg for 14 and 21 days.

The results obtained indicate the absence of direct genotoxic effects of UDMH on the nuclear DNA of leukocytes; hepatocytes; and brain cells of white rats. The oxidative damage to DNA in hepatocytes is apparently associated with a high level of oxidative metabolism of UDMH in the liver after administration at a dose of 20 mg/kg; which is confirmed by pathomorphological studies.