Document Detail


Metabolism and pharmacokinetics of N'-nitrosonornicotine in the patas monkey.
MedLine Citation:
PMID:  12228188     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
N'-Nitrosonornicotine (NNN) is present in significant quantities in tobacco and tobacco smoke and is believed to play an important role as a cause of cancer in people who use tobacco products. Biomarkers of NNN uptake in humans such as urinary metabolites would be useful for assessing cancer risk. Previous studies, carried out almost exclusively in rodents, have characterized urinary metabolites of NNN, but none of these would be suitable as a biomarkers of NNN uptake in humans. Therefore, we studied NNN metabolism in the patas monkey. Monkeys were treated intravenously with [5-(3)H]NNN, which has tritium in the pyridine ring. Blood and urine samples were collected at timed intervals. Six urinary metabolites were observed by high-performance liquid chromatography (HPLC) and were identified by their spectral properties and/or comparison to appropriate standards as follows: metabolite (% of radioactivity eluting from HPLC +/- S.D., n = 3 monkeys); 4-hydroxy-4-(3-pyridyl)butyric acid (43.8 +/- 4.0); 4-oxo-4-(3-pyridyl) butyric acid (2.7 +/- 0.66); norcotinine (13.1 +/- 2.7); norcotinine-1N-oxide (16.5 +/- 1.3); 3'-hydroxynorcotinine (16.9 +/- 2.0); 3'-(O-beta-D-glucopyranuronosyl)hydroxynorcotinine (5.4 +/- 1.0); and unchanged NNN (0.63 +/- 0.15). The two major metabolites in serum were 4-hydroxy-4-(3-pyridyl)butyric acid and norcotinine. NNN was rapidly metabolized to 4-hydroxy-4-(3-pyridyl)butyric acid, whereas the formation of norcotinine and 3'-hydroxynorcotinine were somewhat delayed. The results of this study demonstrate substantial differences between NNN metabolism in the rodent and patas monkey. Metabolism of NNN to norcotinine and its derivatives was far more prevalent in the patas monkey than in the rat. 3'-Hydroxynorcotinine and its O-glucuronide may be formed from NNN via alpha-oximinonornicotine or isomyosmine. There was no evidence that it was formed via norcotinine, although this pathway could not be excluded. 3'-Hydroxynorcotinine could potentially be a biomarker of NNN uptake in humans.
Authors:
Pramod Upadhyaya; Cheryl L Zimmerman; Stephen S Hecht
Related Documents :
10511268 - Biomarkers of dose and susceptibility in cyclists exposed to monoaromatic hydrocarbons.
12044678 - Succinate synthesis and excretion by penicillium simplicissimum under aerobic and anaer...
7810688 - Acute acidosis inhibits liver amino acid transport: no primary role for the urea cycle ...
9737418 - The fate of ingested glyceran esters of condensed castor oil fatty acids [polyglycerol ...
9715398 - Tiaprofenic acid inhibits mucosal prostaglandin e2 synthesis without delaying experimen...
17650308 - Intramyocellular lipid kinetics and insulin resistance.
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  30     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  2002 Oct 
Date Detail:
Created Date:  2002-09-13     Completed Date:  2003-02-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1115-22     Citation Subset:  IM    
Affiliation:
University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Erythrocebus patas
Male
Nitrosamines / chemistry,  pharmacokinetics*,  urine
Grant Support
ID/Acronym/Agency:
CA-44377/CA/NCI NIH HHS; CA-81301/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Nitrosamines; 80508-23-2/N'-nitrosonornicotine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Interindividual variability and tissue-specificity in the expression of cytochrome P450 3A mRNA.
Next Document:  Cefazolin administration and 2-methyl-1,3,4-thiadiazole-5-thiol in human tissue: possible relationsh...