Denitrosation of N-Nitrosodimethylamine in the Rat in Vivo

The potent hepatocarcinogen N-nitrosodimethylamine (NDMA) has been shown to be metabolized by liver microsomes from acetone-induced rats via two pathways (Figure 1). While the denitrosation pathway has been studied fairly extensively in vitro (Keefer et al., 1987b; Wade et al., 1987; Amelizad et al., 1988), only a few tentative observations about its course in the intact animal have so far appeared in the literature (Heath and Dutton, 1958; Keefer et al., 1987a; Magee et al., 1988). The easiest and most direct assessment of denitrosation in vivo should come from measuring the extent of conversion of NDMA to MA, if the NDMA is labeled with carbon-14 so that the metabolically produced MA can be differentiated from the endogenous material that is known to be present (Davis and de Ropp, 1961).