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  • Title: N-methylation of phenylpyridines and bispyridyls as a potential toxication route: tissue distribution of azaheterocycle N-methyltransferase activity in the rabbit.
    Author: Godin CS, Crooks PA, Damani LA.
    Journal: Toxicol Lett; 1986 Dec; 34(2-3):217-22. PubMed ID: 3798480.
    Abstract:
    The in vitro N-methylating capability of rabbit tissue cytosolic preparations, utilizing S-adenosyl-L-[methyl-3H]methionine as methyl donor, is described. Dialysed preparations from the lung, liver and kidney are capable of N-methylating 3- and 4-phenylpyridines and 3,3'- and 4,4'-bispyridyls; the corresponding 2-substituted derivatives are not substrates. With all the four substrates, azaheterocycle N-methyltransferase activity decreased in the order lung greater than kidney greater than liver; the activity in the lung was manifold greater than in the kidney and the liver. Azaheterocycle N-methyltransferase activity could not be detected in the brain cytosol under the enzyme assay conditions used. The production of N-methylpyridinium ion metabolites in the lung, from 4-phenylpyridine, 4,4'-bispyridyl and other pyridino-compounds present in tobacco smoke, may contribute to the observed pulmonary toxicity in tobacco users.
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