Selective sensitivity to tiazofurin of human leukemic cells.
This study reports the selective sensitivity to tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide, NSC-286193) of human leukemic leukocytes as compared to normal ones in bone marrow and peripheral blood samples by comparing the production of the active metabolite, thiazole-4-carboxamide adenine dinucleotide (TAD), from labeled tiazofurin and the depression of GTP concentration. When labeled tiazofurin was incubated with leukocytes obtained from healthy volunteers or from leukemic patients (acute non-lymphocytic leukemia or acute lymphoblastic leukemia), the TAD production was 27.0 +/- 8.3, 551.3 +/- 71.8 and 755.9 +/- 94.1 pmoles/10(9) cells per hr, respectively. Thus, the leukemic cells produced over 20-fold higher concentrations of TAD than the normal leukocytes. Incubation with tiazofurin in leukemic leukocytes decreased the GTP pools (to 48-79%), whereas there was no change in the normal leukocytes. These results indicate a selectivity of response to tiazofurin in human normal and leukemic leukocytes. The procedure reported in this work may be suitable as a rapid predictive test for the sensitivity of leukemic leukocytes to tiazofurin. Such a diagnostic test should be helpful in identifying neoplastic cells sensitive to tiazofurin in the Phase II trials now being developed.
D000227:Adenine Nucleotides / Q000378:metabolism; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000378:metabolism*; D005260:Female; D006160:Guanosine Triphosphate / Q000032:analysis; D006801:Humans; D007938:Leukemia / Q000032:analysis / Q000188:drug therapy / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D012263:Ribonucleosides / Q000378:metabolism*
D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D012263:Ribonucleosides; D012254:Ribavirin; C038167:thiazole-4-carboxamide adenine dinucleotide; D006160:Guanosine Triphosphate; C033706:tiazofurin