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Title: Metabolite signatures in hydrophilic extracts of mouse lungs exposed to cigarette smoke revealed by 1H NMR metabolomics investigation

Herein, 1H-NMR metabolomics are carried out to evaluate the changes of metabolites in lungs of mice exposed to cigarette smoke. It is found that the concentrations of adenosine derivatives (i.e. ATP, ADP and AMP), inosine and uridine are significantly fluctuated in the lungs of mice exposed to cigarette smoke compared with those of controls regardless the mouse is obese or regular weight. The decreased ATP, ADP, AMP and elevated inosine predict that the deaminases in charge of adenosine derivatives to inosine derivatives conversion are altered in lungs of mice exposed to cigarette smoke. Transcriptional analysis reveals that the concentrations of adenosine monophosphate deaminase and adenosine deaminase are different in the lungs of mice exposed to cigarette smoke, confirming the prediction from metabolomics studies. We also found, for the first time, that the ratio of glycerophosphocholine (GPC) to phosphocholine (PC) is significantly increased in the lungs of obese mice compared with regular weight mice. The ratio of GPC/PC is further elevated in the lungs of obese group by cigarette smoke exposure. Since GPC/PC ratio is a known biomarker for cancer, these results may suggest that obese group is more susceptible to lung cancer when exposed to cigarette smoke.
Authors:
 [1] ;  [2] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [3] ;  [1]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Chinese Academy of Sciences, Wuhan (China)
  3. Chinese Academy of Sciences, Wuhan (China)
Publication Date:
OSTI Identifier:
1208733
Report Number(s):
PNNL-SA--102290
Journal ID: ISSN 2153-0769; 47841; 400412000
Grant/Contract Number:
AC05-76RL01830
Type:
Accepted Manuscript
Journal Name:
Journal of Postgenomics Drug & Biomarker Development
Additional Journal Information:
Journal Volume: 05; Journal Issue: 02; Journal ID: ISSN 2153-0769
Research Org:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES Environmental Molecular Sciences Laboratory: H-NMR metabolomics; mouse lungs; cigarette smoke; PCA; OPLS; obesity