Hepatocyte initiation during continuous administration of diethylnitrosamine and 1,2-sym-dimethylhydrazine

Hepatocyte initiation, as indexed by growth-selected gamma-glutamyl transferase-positive foci, was measured during continuous exposure to diethylnitrosamine (DEN) at concentrations used in previous DEN bioassay, DNA adduct, and cell replication studies. Hepatocyte initiation increased in a dose- and lobe-specific manner. The efficiency of DEN as an initiating agent was not affected by DEN dose rate over concentrations ranging from 4 to 40 ppm. In a similar experiment the initiating abilities of 1,2-sym-dimethylhydrazine and DEN were compared under continuous exposure regimens. Foci induction increased in a lobe- and time-dependent manner. When left and median lobes were compared, the initiating ability of the two compounds correlated with their carcinogenicity. However, when corresponding anterior lobes were compared, no such correlation was observed.