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The mechanism of carcinogenic action of 1,2‐dimethylhydrazine (sdmh) in rats
Author(s) -
Pozharisski K. M.,
Kapustin Yu. M.,
Likhachev A. J.,
Shaposhnikov J. D.
Publication year - 1975
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910150417
Subject(s) - carcinogen , kidney , metabolite , intestinal mucosa , gastrointestinal tract , chemistry , medicine , urine , glucuronide , metabolism , endocrinology , biology , biochemistry
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.