[13N]Ammonia and L-[amide-13N]glutamine metabolism in glutaminase-sensitive and glutaminase-resistant murine tumors.

摘要: The short-term metabolic fate of labeled nitrogen derived from [13N]ammonia or l-[amide-13N]glutamine was determined in murine tumors known to be resistant (Ridgeway Osteogenic Sarcoma (ROS)) sensitive (Sarcoma-180 (S-180)) glutaminase therapy. At 5 min after intraperitoneal injection l-[amide-13N]glutamine, only about 0.7% the label recovered both protein and nucleic acid. After administration, most (over 80%) a metabolized form; large portion this (50–57%) urea fraction with smaller amount glutamine (37–42%). major incorporation into components cycle amounts acidic metabolites amino acids. No found during vitro studies which S-180 tumor slices were incubated [13N]ammonia, suggesting that [13N]urea formed vivo experiments not due de novo synthesis through carbamyl phosphate tumor. Both exhibited very low synthetase activity. Following treatment, γ-glutamyltransferase activities, while remaining low, increased but tumor; increase may related insensitivity ROS toward treatment.