HEPATIC UDP-GLUCURONYLTRANSFERASE IN WISTAR AND GUNN RATS - IN VITRO ACTIVATION BY DIETHYLNITROSAMINE

Dutton (1966) has previously pointed out that it is difficult to assess the absolute UDP-glucuronyltransferase activity in different tissues, there being little known of the in vitro factors regulating the activity of this enzyme. Investigations are further complicated by lack of studies on solubilised transferase and by the presence, in many tissues, of UDPGA-destroying pyrophosphatases. The results in this paper demonstrate, nevertheless, that hepatic UDP-glucuronyltransferase from Wistar and Gunn rats may be activated in vitro by the carcinogen diethylnitrosamine (DEN). The stimulatory effect appears to be confined to rat liver and is particularly marked with Gunn rat liver preparations - to the extent that the reported transferase deficiency of this tissue (Schmid et al, 1958; Lathe and Walker, 1958) is no longer apparent when DEN is included in the assay system. DEN-activation occurs with both microsomal and solubilised transferase and may be demonstrated using either o-aminophenol or paracetamol as substrate. Kinetic analysis of the activation indicates that DEN does not alter the affinity of the enzyme for substrate. © 1968.