Changes in the Fine Structure of Rat Liver Cells Brought about by Dimethylnitrosamine

Dimethylnitrosamine (DMNA) acts as a hepatic carcinogen (1) and causes an inhibition of amino acid incorporation into rat liver protein ,in vivo (2). The latter effect could also be demonstrated (3) in vitro using slices or the microsomalsoluble fraction prepared from livers of rats as early as 3 hours after intravenous administration of DMNA (50 mg./kg, body weight). The lesion appeared to be specific in so far as respiration, glycolysis, and 2 microsomal-bound enzymes were not affected (3). Inhibition of amino acid incorporation could also be accomplished in liver slices of normal rats by adding DMNA in vitro (3). On account of indirect evidence it was suggested (3) that DMNA by itself was not toxic, but that it was converted by one of the N-demethylating enzymes of liver microsomes to a toxic derivative; i.e. the methylol derivative of DMNA or formaldehyde liberated therefrom, which reacted in particular with susceptible groups of the microsomes and thus blocked the amino acid incorporation process. The present report is concerned with the effect of DMNA on the fine structure of liver cells in order to find a possible correlation between the biochemical lesion and the submicroscopic organization of the endoplasmic reticulum (ER).