Metabolism of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone by Cultured Monkey Lung Explants

The metabolism of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was investigated in short-term cultures of monkey lung. Explants from the lungs of two patas monkeys ( Erythrocebus patas ) and one cynomolgus monkey ( Macaca fascicularis ) were incubated with 10 μM [5- 3 H]NNK and aliquots were analyzed for NNK metabolites by HPLC at various time points from 1 to 24 h. F344 rat lung tissue metabolism of NNK was assayed under the same conditions. Substantial amounts of metabolites from the α-hydroxylation metabolic activation pathway were detected in all cultures. In two of the monkey lung cultures, these metabolite levels were significantly higher than those formed by other pathways. All cultures also metabolized NNK by pyridine- N- oxidation and carbonyl reduction. The metabolism of NNK by cultured monkey lung was generally similar to that observed in rat lung, indicating that there are not major species differences between rodents and nonhuman primates in pulmonary metabolism of NNK.