Abstract
The radioactivity level in blood, bile, urine and contents of parts of the gastro‐intestinal tract in rats was studied after subcutaneous administration of ^3^H‐1,2‐dimethylhydrazine (^3^H‐SDMH) which induces colonic tumours. The alkylation of DNA, RNA and protein in the intestinal mucosa, liver and kidneys was estimated 1 h to 28 days after ^3^H‐SDMH treatment from the ^3^H‐incorporation into these macro‐molecules. Administration of ^3^H‐1,2‐diethylhydrazine (^3^H‐SDEH) which does not induce intestinal tumours was made as a control. Fifteen to 30 min after ^3^H‐SDMH treatment, marked radioactivity was found in blood, bile, urine and in contents of all regions of gastro‐intestinal tract. After ^3^H‐SDMH administration no label occurred in the contents of localized segments of gastro‐intestinal tract although it was present in blood, bile and urine. ^3^H‐SDMH methylated DNA, RNA and proteins of intestinal mucosa, liver and kidney to a high degree. One hour after ^3^H‐SDMH treatment the incorporation of label into protein of intestinal mucosa was higher than into liver and kidneys. ^3^H‐SDEH did not alkylate macromolecules in these organs but did so in thymus, spleen and brain, which are target organs for this carcinogen. After total hepatectomy. ^3^H‐SDMH did not methylate macromolecules of the intestinal mucosa. The following mechanism for the carcinogenic effect of SDMH is suggested. A carcinogenic metabolite of SDMH forms, in the liver, a conjugate with glucuronic acid. This glucuronide enters the gut both with bile and directly via the circulation. Microbial β‐glucuronidase releases the active metabolite which, in turn, alkylates tissue macro‐molecules.