Pyrimidine pathways enzymes in human tumors of brain and associated tissues: potentialities for the therapeutic use of N-(phosphonacetyl-L-aspartate and 1-beta-D-arabinofuranosylcytosine.
The activities of aspartate transcarbamylase (de novo pyrimidine biosynthesis pathway) and of deoxycytidine kinase as well as deoxycytidine deaminase (salvage pyrimidine biosynthesis pathway) were determined in extracts prepared from 40 brain tumors of different types in comparison with extracts from normal nervous tissues. Aspartate transcarbamylase, which is undetectable in normal brain tissue, is present in all tumor samples and in some cases rises to very high activities. Deoxycytidine kinase activity is present in all tissues but its level is generally higher in tumors. Deoxycytidine deaminase is present in all the tissues which were analyzed, although its activity is lower in some of the tumor samples. 1-beta-D-Arabinofuranosylcytosine is a substrate for both deoxycytidine kinase and deaminase in all the samples used except one. These results suggest some potential for the utilization of 1-beta-D-arabinofuranosylcytosine and N-(phosphonacetyl)-L-aspartate in the treatment of brain tumors.
Madani
S
S
Institut de Neurologie, La Rabta, Tunis, Tunisia.
Baillon
J
J
Fries
J
J
Belhadj
O
O
Bettaieb
A
A
Ben Hamida
M
M
Hervé
G
G
D001221:Aspartate Carbamoyltransferase / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D001921:Brain / Q000201:enzymology; D001932:Brain Neoplasms / Q000201:enzymology*; D003561:Cytarabine / Q000378:metabolism* / Q000627:therapeutic use; D003564:Cytidine Deaminase; D006801:Humans; D008577:Meningeal Neoplasms / Q000201:enzymology; D009700:Nucleoside Deaminases / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010770:Phosphotransferases / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism
D011743:Pyrimidines; D003561:Cytarabine; D001224:Aspartic Acid; C013195:sparfosic acid; D001221:Aspartate Carbamoyltransferase; D010770:Phosphotransferases; C019979:cytidylate kinase; D009703:Nucleoside-Phosphate Kinase; D009700:Nucleoside Deaminases; D003564:Cytidine Deaminase; C011530:deoxycytidine deaminase; D010746:Phosphonoacetic Acid