[Metabolic activation of N-methyl-N-nitrosourea in tumor cells]

An enzymatic activation of N-methyl-N-nitrose urea (MNU) was studied in microsomes, isolated from hepatoma 22a ascites cells, using a procedure which enabled to reveal the MNU enzymatic activation in mice liver microsomes. The MNU metabolic activation was not observed in hepatoma cell microsomes; at the same time, the MNU activation occurred when the cells were incubated under conditions of a suspension culture. The enzymes, participating in metabolic activation of MNU, were apparently arranged at the surface of the tumoral cells. Alkylation of MNU macromolecules was shown to be a two-step process. At the first step alkylation was due to spontaneous degradation of MNU and at the second step it was responsible for formation of active products as a result of MNU metabolic activation. MNU appears to induce synthesis of enzymes required of its metabolic activation in hepatoma 22a cells within 30 min.