MK 886, an antagonist of leukotriene generation, inhibits DNA synthesis in a subset of acute myeloid leukaemia cells.
We have studied the actions of inhibitors of leukotriene generation on DNA synthesis (measured by 3H-thymidine incorporation) in blast cells from patients with acute myeloid leukaemia (AML). Cells from a subset only of these patients were sensitive to MK 886, a potent selective inhibitor of leukotriene synthesis. By contrast, DNA replication in cells from all of the patients was inhibited by nordihydroguiaretic acid (NDGA), a leukotriene synthesis inhibitor of lower selectivity. DNA synthesis in normal bone marrow cells and phytohaemagglutinin-stimulated lymphocytes was sensitive to NDGA but not to MK 886. The data suggest that NDGA inhibits DNA replication by a mechanism other than the abolition of leukotriene biosynthesis, but that DNA synthesis in a subset of AML cells may be dependent on the generation of lipoxygenase products, as indicated by sensitivity to MK 886.
Khan
M A
MA
Department of Haematology, Royal Free Hospital Medical School, London, U.K.
Hoffbrand
A V
AV
Mehta
A
A
Wright
F
F
Tahami
F
F
Wickremasinghe
R G
RG
D000328:Adult; D000368:Aged; D002648:Child; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000473:pathology; D020024:Leukotriene Antagonists; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D008875:Middle Aged; D002722:Chlorobenzenes
D004273:DNA, Neoplasm; D007211:Indoles; D020024:Leukotriene Antagonists; D009637:Masoprocol; C060893:MK-886; D002722:Chlorobenzenes