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Hepatocyte Initiation during Continuous Administration of Diethylnitrosamine and 1,2-sym-Dimethylhydrazine¹

Departments of Biochemical Toxicology and Pathobiology [F. C. R., J. A. B., F. H. D., J. A. S.] and Epidemiology [P. H. M.], Chemical Industry Institute of Toxicology, Research Triangle Par, North Carolina 27709

Hepatocyte initiation, as indexed by growth-selected -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.

¹ Supported in part by United States Public Health Service Grant CA07588-01A1 awarded by National Cancer Institute, Department of Health and Human Services.

² Present address: Management Information Services Department, Glaxo, Inc., 5 Moore Drive, Research Triangle Park, NC 27709.

³ To whom requests for reprints should be addressed, at Chemical Industry Institute of Toxicology, Department of Biochemical Toxicology and Pathobiology, P. O. Box 12137, Research Triangle Park, NC 27709.

Received 7/20/87. Revised 10/21/87. Accepted 11/11/87.