The stoichiometric fate of AZASERINE (cas 115-02-6) metabolized in vitro by tissues from AZASERINE (cas 115-02-6)-treated dogs and mice☆

Add time:08/30/2019    Source:sciencedirect.com

The in vitro metabolism of AZASERINE (cas 115-02-6) was determined in various tissues of mouse, dog, and rat with the aim of elucidating the stoichiometric relationship of azaserine transformation with the production of pyruvate, ammonia and glycolic acid. The influence of in vivo treatment with azaserine and ethyldiazoacetate on the in bitro metabolism of azaserine was also monitored in order to uncover any correlation between azaserine metabolism and histopathology. The stoichiometry of azaserine disappearance and pyruvate and ammonia formation was confirmed for mouse liver and demonstrated for dog tissues. Identification and stoichiometric production of glycolic acid as the 2-carbon moiety associated with the diazo group was established. The most active tissues in the dog were salivary and prostrate tissues which undergo morphological alteration after in vivo treatment with azaserine. In both azaserine and ethyldiazoacetate-treated dogs and mice the activity of the azaserine degrading enzyme was inhibited. Ethyldiazoacetate was less toxic and did not cause microscopic changes, and salivary lesions were absent in the mice treated with either drug.

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