[1,2-13C2]-D-glucose profiles of the serum, liver, pancreas, and DMBA-induced pancreatic tumors of rats.
OBJECTIVE
In vitro stable isotope glucose tracer studies indicate that undifferentiated cells of the pancreas use glucose primarily through the nonoxidative reactions of the pentose cycle for nucleic acid ribose synthesis, whereas normal or less transformed cells primarily use the oxidative branch of the cycle.


METHODS
The pancreatic heads of 4 groups (5/group) of male rats were implanted with time-release pellets designed to deliver placebo or 7,12-dimethylbenzanthracene (DMBA) at 11, 33, or 56 mg/d. Four weeks after pancreatic exposure to DMBA, [1,2-C2]-D-glucose tracer (1 g/kg) was injected intraperitoneally followed by sera collection at 1 and 2 hours and harvest of tumors, adjacent pancreatic tissue, and sera at 3 hours.


RESULTS
Tumors (2-9 mm) were found across DMBA groups, with the largest in the high-dose group (> or =5 mm). Selective monitoring by gas chromatography-mass spectrometry of the doubly-labeled [1,2-C2]-D-ribose of RNA, which requires nonoxidative synthesis in the pentose cycle, showed a 2.8-, 2.9-, and 5.7-fold increase in pancreatic tumors. Liver and adjacent pancreas preferentially produced [1-C1]-D-ribose through the oxidative reactions of the cycle. Tumor-bearing animals also cleared and recycled tracer glucose at a faster rate.


CONCLUSIONS
Simultaneous selective positional ion monitoring of C-labeled metabolites and their mass isotopomers in tissues and blood opens new avenues for the early detection and response to therapy testing of pancreatic cancer using GC-MS and/or magnetic resonance imaging-based methods. This study emphasizes the benefits of stable isotope-based dynamic metabolic profiling, when applied in vivo, and the several advantages it offers to positron emission tomography.
Boros
László G
LG
SIDMAP, LLC, and Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA. boros@labiomed.org
Lerner
Megan R
MR
Morgan
Daniel L
DL
Taylor
Stephanie L
SL
Smith
Brenda J
BJ
Postier
Russell G
RG
Brackett
Daniel J
DJ
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002247:Carbon Isotopes; D005947:Glucose / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D002247:Carbon Isotopes; D015127:9,10-Dimethyl-1,2-benzanthracene; D012313:RNA; D005947:Glucose