Effect of 6-azauridine and pyrazofurin on fibrinolysis by L1210 leukemic cells.
The expression of plasminogen activator activity (PA) by L1210 leukemic ascitic cells, obtained from the peritoneum of BDF1 mice, increases in the terminal stages of the disease. Treatment of mice carrying advance leukemia (day 6 following inoculation with 10(6) cells i.p.) with 6-azauridine (AzUR) results in prolonged survival (2-3 days) and also in increased expression of PA activity by the ascitic cell population. Similar treatment with pyrazofurin (PF), another inhibitor of orotidylate decarboxylase and of de novo pyrimidine synthesis, fails to produce either of these effects. Neither AzUR or PF, given at the early stage of tumor growth (day 3), extend the life span nor do they cause increase of the PA activity. Thus, the elevation in PA activity following treatment with AzUR is associated with the asymptotic stage of the disease and this phenomenon correlates positively with the life-prolonging effects of this drug. An analysis of the PA activity elicited by intact cells, secretions, and cellular digests suggests that most of the activity originates on the surface of the cells. The results indicate that the described in vivo effect of AzUR, but not that of PF, on late-stage leukemia, is mediated by the changes in the fibrinolytic potential of the tumor or host cells rather than through the inhibition of the de novo pyrimidine synthesis.
D000577:Amides; D000818:Animals; D001380:Azauridine / Q000494:pharmacology*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D007939:Leukemia L1210 / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000037:antagonists & inhibitors; D010960:Plasminogen Activators / Q000378:metabolism; D011720:Pyrazoles; D011743:Pyrimidines / Q000096:biosynthesis; D012263:Ribonucleosides / Q000494:pharmacology*; D012266:Ribose; D012510:Sarcoma 180 / Q000188:drug therapy; D013997:Time Factors
D000577:Amides; D011720:Pyrazoles; D011743:Pyrimidines; D012263:Ribonucleosides; C002997:pyrazofurin; D012266:Ribose; D001380:Azauridine; D010960:Plasminogen Activators; D009964:Orotidine-5'-Phosphate Decarboxylase