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 μM [5-3H]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.
Footnotes
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Send reprint requests to: Stephen S. Hecht, Ph.D., University of Minnesota Cancer Center, Box 806 Mayo, 420 Delaware St. SE, Minneapolis, MN 55455. E-mail: hecht002{at}tc.umn.edu
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This study was supported by Grants CA-44377 and CA-81301 from the National Cancer Institute.
- Abbreviations used are::
- NNK
- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
- NNAL
- 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol
- NNAL-Gluc
- [4-(methylnitrosamino)-1-(3-pyridyl)but-1-yl]-β-O-d-glucosiduronic acid
- NNAL-N-oxide
- 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanol
- keto alcohol
- 4-hydroxy-1-(3-pyridyl)-1-butanone
- diol
- 4-(3-pyridyl)butan-1,4-diol
- keto acid
- 4-oxo-4-(3-pyridyl)butanoic acid
- hydroxy acid
- 4-hydroxy-4-(3-pyridyl)butanoic acid
- NNK-N-oxide
- 4-(methylnitrosamino)-1-(3-pyridyl-N-oxide)-1-butanone
- Received July 1, 1999.
- Accepted September 23, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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