Dimethylnitramine metabolism in vitro by NZR rat liver slices

The net metabolism of dimethylnitramine (DMNO) was studied in NZR rat liver slices in tissue culture medium (Dulbecco's MEM). In rats, mice and fish, liver is the principal target organ for DMNO carcinogenesis. Destruction of DMNO in vitro with oxygenated medium was linear with amount of tissue (0.3-3.0 g liver), and with substrate concentration (0.14-4.44 mM). Substrate destruction (initially 0.2 mM DMNO) was linear for 60 min (average rate 0.9 +/- 0.1 microgram DMNO/g liver/min) and then slowed to become linear again at about half the initial rate from 90 min to longer than 5 h. In anoxic (N2) conditions DMNO metabolism slowed or stopped completely after 70 min. Metabolism of dimethylnitrosamine (DMN) was studied in the same preparation. DMN destruction rates were initially about 50% higher than DMNO, but were equal at longer incubation times. Simultaneous metabolism of DMNO and DMN by the same tissue slices showed DMNO rates unaltered in the presence of equimolar DMN (0.24 mM), but DMN rates were 20-40% depressed. No evidence was found for the oxidation of DMN to form DMNO, or for reduction of DMNO to DMN.