DIFFERENT POSITIONAL ACCUMULATION OF [1,2-13C2] GLUCOSE INTO RNA RIBOSE OF DMBA-INDUCED PANCREATIC TUMORS, PANCREAS AND LIVER.

Abstract

Background: Early diagnosis of pancreatic cancer is critical to timely initiate adequate treatment in order to prolong life. Method: In this study pancreatic cancer was induced by the implantation of 1, 3 or 5 mg DMBA pellets into the head of the pancreas of male Wistar rats. After 1 month the [1,2-13 C2]glucose tracer at 1 g/kg dose was given via i.p. injection 3 hrs prior to harvest of tumors, adjacent pancreas, liver and blood serum. Gas chromatography and mass spectrometry (GC/MS) was used to determine the positional incorporation of the 13C tracer carbon of glucose into RNA ribose, palmitate, stearate and oleate of the organs, as well as serum glucose and lactate. Results: There was a dose dependent increase in total 13C tracer accumulation into RNA ribose of tumors, indicated by ∑mn values of 0.74 (placebo control), 0.83, 0.85 and 0.94* (n=5; *P<0.05; #P<0.001), respectively. Selective ion monitoring (SIM) of the doubly 13C labeled ribose species (m2), which requires non-oxidative synthesis via the tumor specific transketolase reaction of the pentose cycle, showed a 2.8*, 2.9* and a 5.7#-fold increase. Although the adjacent pancreas to tumors also showed some increase in total tracer accumulation after 3 and 5 mg DMBA treatment, there was no increase in the doubly 13C labeled ribose moiety. Liver cell positional RNA ribose labeling and total 13C tracer accumulation were not affected by DMBA carcinogenesis of the pancreas. Tumor fatty acid profiles were inconsistent, exhibiting either low or high oleate ratios. Conclusions: This study indicates that chemically induced tumors of the pancreas of Wistar rats exhibit differential 13C labeling patterns in RNA ribose from that of the adjacent pancreas and liver when [1,2-13C2] glucose is used as the tracer. This may open new avenues for the early detection and response-to-therapy testing of this cancer, using 13C based magnetic resonance imaging (MRI) and GC/MS based serum/urine tests selectively monitoring 13C sugar moieties in pancreatic tissues and body fluids simultaneously.