Enzymatic activation of the carcinogens 2-phenylethylhydrazine and 1,2-dimethylhydrazine to carbon-centered radicals.
Spin-trapping experiments demonstrate that oxidation of 1,2-dimethylhydrazine and 2-phenylethylhydrazine generates a comparable yield of carbon-centered radicals when catalyzed by horseradish peroxidase - H2O2. Using oxyhemoglobin as the catalyst, 2-phenylethylhydrazine oxidation generates ten times more carbon-centered radicals than 1,2-dimethylhydrazine oxidation. This result is in agreement with oxygen consumption studies from which the apparent KM values of 8.0 mM and 72 mM were calculated for the oxyhemoglobin-catalyzed oxidation of 2-phenylethylhydrazine and 1,2-dimethylhydrazine, respectively. These differences in metabolic activation of mono- and disubstituted hydrazines may be of importance regarding the carcinogenic properties of these derivatives.
Netto
L E
LE
Departamento de Bioquímica, Universidade de São Paulo, Brasil.
Leite
L C
LC
Augusto
O
O
D019813:1,2-Dimethylhydrazine; D055598:Chemical Phenomena; D002621:Chemistry; D004127:Dimethylhydrazines / Q000378:metabolism*; D004789:Enzyme Activation; D005609:Free Radicals; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008763:Methylhydrazines / Q000378:metabolism*; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D010659:Phenylhydrazines / Q000378:metabolism*
D004127:Dimethylhydrazines; D005609:Free Radicals; D008763:Methylhydrazines; D010108:Oxyhemoglobins; D010659:Phenylhydrazines; D006735:Horseradish Peroxidase; D010544:Peroxidases; D019813:1,2-Dimethylhydrazine