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Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by cultured monkey lung explants

  1. Author:
    Hecht, S. S.
    Trushin, N.
    Chhabra, S. K.
    Anderson, L. M.
    Nerurkar, P. V.

  2. Author Address

    Hecht SS Univ Minnesota, Ctr Canc Box 806 Mayo,420 Delaware St SE Minneapolis, MN 55455 USA Univ Minnesota, Ctr Canc Minneapolis, MN 55455 USA NCI Frederick, MD 21701 USA Amer Hlth Fdn Valhalla, NY 10595 USA
    1. Year: 2000
  2. Journal: Drug Metabolism and Disposition
    1. 28
    2. 1
    3. Pages: 5-9
  4. Type of Article: Article
  1. Abstract:

    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 mu M [5-H-3]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 alpha-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. [References: 26]

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