IDENTIFICATION OF YLNITROSAMINO)-1-[3-(6-HYDROXYPYRIDYL)]-1-BUTANONE AS A URINARY METABOLITE OF 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN RODENTS

A previously unknown urinary metabolite of 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK) was identified as ylnitrosamino)-1-[3-(6-hyd roxypyridyl)]-1-butanone (6-hydroxyNNK). The metabolite was initially isolated from rat urine. On the basis of its MS and NMR, it was either a 4- or 6-hydroxypyridyl derivative of NNK. Model compounds were synt hesized to distinguish between these possibilities; the results indica ted that the metabolite was 6-hydroxyNNK. This was confirmed by indepe ndent synthesis; the spectral and chromatographic properties of 6-hydr oxyNNK were the same as those of the metabolite. F-344 rats and A/J mi ce treated with 100 mg/kg NNK excreted approximately 1% of urinary met abolites as 6-hydroxyNNK; it was not detected as a sulfate or glucuron ide conjugate. This is the first example of a pyridyl-hydroxylated met abolite of a tobacco-specific nitrosamine. On the basis of comparison to published data on other pyridine derivatives, 6-hydroxyNNK may be f ormed by bacterial metabolism. The potential utility of 6-hydroxyNNK a s a dosimeter of human uptake of NNK is discussed.