Cell proliferation and DNA dependent DNA polymerase estimation in acute lymphoblastic leukaemia during treatment with prednisone and vincristine.
The presence of DNA polymerase and primer-template DNA in lymphoblast nuclei by measuring the in vitro incorporation of 3H-thymidine-5'-triphosphate (3H-TTP) was studied in 10 patients with acute lymphoblastic leukemia. Protein synthesis and various other cytokinetic parameters were also studied. After prednisone (P) administration a marked decrease in 3H-TTP labelling index (3H-TTP LI) was apparent together with an inhibition of 3H-leucine incorporation (3H-LEU LI) into lymphoblasts. A moderate decrease in 3H-TDR labelling index (3H-TDR LI) and a later decrease in mitotic index (MI) were seen. Single cell DNA measurements showed a depletion of 3H-TDR labelled lymphoblasts in early part of S-phase apparent at 24 h lasting up to 54 h after P administration. Vncristine given as a flash injection later in the study period caused an immediate rise of the MI, at the same time the P induced decline in 3H-TTP LI, 3H-TDR LI and 3H-LEU LI were continued in most patients. P is thought to damage the cells both in and outside the cell cycle. In the cell cycle the effect of P is an arresting effect in G1.
D000293:Adolescent; D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy* / Q000201:enzymology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000201:enzymology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D013997:Time Factors; D014750:Vincristine / Q000627:therapeutic use*
D004273:DNA, Neoplasm; D014750:Vincristine; D004259:DNA-Directed DNA Polymerase; D011241:Prednisone