Summary
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.
Zusammenfassung
Die Radioaktivität des Blutes, der Galle und des Inhalts verschiedener Teile des gastrointestinalen Trakts wurde für verschiedene Zeitintervalle bis zu 24 Std nach Injektion von 3H-SDMH abgeschätzt. 65% der Radioaktivität wurde im Harn ausgeschieden. Von den in das Intestinum eintretenden radioaktiven Produkten entstammen 96% der Galle und nur 4% der Zirkulation durch die Wand des Intestinums. Diese letztere, kleine Menge von SDMH Metaboliten spielt eine wichtige Rolle für die Genese der Intestinaltumoren. Dieser Schluß wurde durch die Beobachtung bewiesen, daß sich die intestinalen Tumoren in verschiedenen isolierten Segmenten des Darms entwickelten, für die der Zufluß der Galle ausgeschlossen war, sowie durch Literaturdaten, die zeigen, daß SDMH unverändert in die Galle ausgeschieden wird.
Es wurde gezeigt, daß der carcinogene Effekt vom Dosierungsschema der Carcinogenbehandlung abhängt. Dies ist wahrscheinlich auf Veränderungen des SDMH-Stoffwechsels zurückzuführen; die optimalen Bedingungen zur Induktion intestinaler Tumoren sind nach einmal wöchentlicher Gabe von 21 mg SDMH/kg Körpergewicht gegeben. Hypothetische Stoffwechselwege für SDMH, die zur Tumorbildung führen, werden anhand zugänglicher experimenteller Daten diskutiert.
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Pozharisski, K.M., Shaposhnikov, J.D., Petrov, A.S. et al. Distribution and carcinogenic action of 1,2-dimethylhydrazine (SDMH) in rats. Z. Krebsforsch. 87, 67–80 (1976). https://doi.org/10.1007/BF00285075
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DOI: https://doi.org/10.1007/BF00285075