Genotoxic action of the 1,1-dimethylhydrazine determined by alkylating compounds appearing in the result of oxidation and hydrogen peroxide

Mechanisms of 1,1-dimethylhydrazine (unsymmetrical dimethylhydrazine (UDMH)) toxic action on living systems on the example of a bacterial cell with lux genes-based biosensors are studied. In the present work, hybrid plasmids with bacterial luciferase reportergenes luxCDABE controlled by the stress-inducible promoters are constructed. Cells of Escherichia coli containing these hybrid plasmids are called lux biosensors. Using the obtained lux biosensors that specifically detect oxidative stress, DNA and protein damage, it is shown that PkatG, PcolD (or PrecA) and PalkA are the main promoters induced in response to the UDMH action on the bacterial cells. The activation of PkatG, PcolD promoters in the presence of UDMH is triggered by hydrogen peroxide formed from the reduction of atmospheric oxygen. We demonstrate that the induction of the lux -biosensor E. coli MG1655(pAlkA-lux ) starts with the appearance of products of incomplete oxidation of UDMH (particularlyN-Nitrosodimethylamine), which are strong mutagens similar, in a degree of genotoxicity, to nitrosourea and N-Methlyl-N-nitro-N-nitrosoguanidine.