Irreversible inhibition of the cytosolic metabolism of N-hydroxy-2-acetylaminofluorene by its glycolyl analog.

The glycolyl hydroxamic acid derivative of 2-aminofluorene was found to be a potent inhibitor of its own metabolism and the metabolism of N-hydroxy-2-acetylaminofluorene by rat liver cytosol. The inhibition was irreversible, as well as time and concentration dependent, which indicates a suicide-inhibition type of metabolism. There was a direct correlation between the inhibition of N-hydroxy-2-acetylaminofluorene disappearance and 2-acetylaminofluorene formation. In contrast, both the glycolyl and acetyl hydroxamic acid derivatives were metabolized to a similar extent by enzymes in the microsomal fraction.