INHIBITION OF METABOLISM OF 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE BY DIETARY BENZALDEHYDES

As part of a routine screening assay, benzaldehyde was found to inhibi t 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism. Con sequently, the effects of benzaldehyde and several structurally relate d compounds on NNK metabolism were examined in murine hepatic and pulm onary microsomes. All test compounds inhibited formation of the metabo lites 4-oxo-4-(3-pyridyl)butyric acid (OPBA), 4-hydroxy-1-(3-pyridyl)- 1-butanone (HPB), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (N NAL) in hepatic microsomes and inhibited formation of ethylnitrosamino )-1-(3-pyridyl-N-oxide)-1-butanone (NNK N-oxide), HPB, and NNAL in pul monary microsomes. m-Anisaldehyde was the most potent inhibitor, and p -hydroxybenzaldehyde and syringaldehyde were less potent than benzalde hyde and vanillin in inhibiting the formation of OPBA and HPB, NNK met abolites that reflect metabolic activation (alpha-hydroxylation). Vani llin was essentially as potent as benzaldehyde. The mechanism of inhib ition exhibited by these compounds appears to be competitive in nature . The ability of these compounds to inhibit NNK activation suggests th at these compounds may be effective blocking agents (anti-initiating a gents) for NNK lung tumorigenesis.