title: Untargeted polar metabolomics of transformed MDA-MB-231 breast cancer cells expressing varying levels of human arylamineN-acetyltransferase 1.
abstract: BACKGROUND
  Human arylamineN-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. Expression of NAT1 is elevated in several cancers including breast cancer. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear.
  
  
  OBJECTIVE
  This study explored polar metabolome differences between MDA-MB-231 breast cancer cells expressing varying levels of NAT1 activity using an untargeted approach.
  
  
  METHODS
  Three MDA-MB-231 breast adenocarcinoma cell lines that stably express wild-type, increased, and decreased levels of human NAT1 were investigated for differences in polar metabolic profile using a comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF MS) system.
  
  
  RESULTS
  Increased levels of human NAT1 in the transformed cell lines resulted in a statistically significant decreased abundance of the metabolite palmitoleic acid (q = 0.0006), when compared to normal and decreased levels of human NAT1. The fatty acid synthesis pathway utilizes acetyl coenzyme A (acetyl-CoA) in the first two reactions of the pathway and eventually leads to the synthesis of palmitoleic acid.
  
  
  CONCLUSIONS
  These data suggest a link between increased levels of NAT1 activity and decreased flux of acetyl-CoA through this portion of the fatty acid synthesis pathway.
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Samantha M
authors.initials: SM
authors.lastname: Carlisle
authors.affiliation: Department of Cardiovascular Medicine, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Trainor
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Doll
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Marcus W
authors.initials: MW
authors.lastname: Stepp
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: States
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Hein
keywords: Acetyl-CoA; Breast Cancer; Metabolomics; NAT1; Palmitoleic Acid