Enzymes of the de novo and salvage pathways for pyrimidine biosynthesis in normal colon, colon carcinoma, and xenografts

摘要: Since current methods of chemotherapy for adenocarcinoma the colon are essentially ineffective, this study was designed to test enzymatic differences between tumors and normal that might form basis more effective treatment. Human tumor xenografts also were examined found be very similar primary when tested for: uridine-cytidine (Urd-Cyd) kinase orotidine 5'-phosphate (OMP) decarboxylase activity, apparent Michaelis constants Urd, ATP, OMP, temperature pH optima Urd-Cyd kinase. However, enzyme activity levels varied from one xenograft line another, these could not correlated with growth rate or sensitivity 5-fluorouracil (5-FU). The xenograft, therefore, may provide a suitable model human colorectal adenocarcinoma, but care must taken screen different lines in order select ones comparable tumors. Primary xenografts, compared colon, have significantly higher specific activities enzymes both de novo salvage pathways uridine monophosphate (UMP) biosynthesis. OMP greater by 132% 91%, respectively, 186% 63%, xenografts. Consequently, treatment using inhibitors pyrimidine nucleotide biosynthesis would probably require combination compound inhibits pathway, e.g., kinase, pyrazofurin N-(phosphonacetyl)-L-aspartate (PALA).