Distribution and carcinogenic action of 1,2-dimethylhydrazine (SDMH) in rats

Abstract

The radioactivity in the blood, bile, and contents from different parts of the gastro-intestinal tract was estimated for different time intervals up to 24 h after 3H-SDMH injection to rats. 65% of the radioactivity was excreted in the urine. Of the total quantity of radioactive products entering the intestine, 96% is brought with bile and only 4% from the circulation through the wall of the intestine. This latter small amount of SDMH metabolites plays a leading role in the genesis of intestinal tumours. This conclusion was proved by the observation that the intestinal tumours developed in different isolated segments of the gut where the entry of bile was excluded and by published data indicating that SDMH is excreted unchanged in the bile. It was shown that the carcinogenic effect depends upon the dose schedule of carcinogen treatment, probably, due to the changes in the SDMH metabolism. The optimal conditions for induction of intestinal tumours occur after administration of SDMH in a dose of 21 mg/kg body weight once a week. Hypothetic SDMH metabolic pathways leading to tumour production have been considered in the light of available experimental data.