Variation in iron accumulation, transferrin membrane binding and DNA synthesis in the K-562 and U-937 cell lines induced by chelators and their iron complexes.
Eight chelators - 8-hydroxyquinoline, 1-hydroxypyridine-2-thione (omadine), tropolone, pyridoxal isonicotinoyl hydrazone, 2-methyl-3-hydroxypyr-4-one (maltol), 1-methyl-3-hydroxypyrid-2-one, 1,2-dimethyl-3-hydroxypyrid-4-one and mimosine--and their iron complexes were tested on cells of the established human tumour cell lines K-562 (erythroleukaemic) and U-937 (monoblastoid) for their effects on a) cellular accumulation of iron provided by transferrin (Tf) via receptor-mediated endocytosis, b) specific cell surface binding of Tf, c) cell viability and, d) DNA synthesis. The lipophilic chelators suppressed the accumulation of Tf-supplied iron in the K-562 cells and less so in the U-937 cells, whereas the effects of the other chelators were closer to control range. The lipophilic chelators pyridoxal isonicotinoyl hydrazone, tropolone, 8-hydroxyquinoline and omadine were found to be cytotoxic in this order, with the U-937 being generally more sensitive than K-562. The presence of iron diminished the toxicity. The DNA synthesis was also affected, from a partial suppression in K-562 to a slight increase in U-937 in the presence of pyridoxal isonicotinoyl hydrazone and to strong suppression with 8-hydroxyquinoline and omadine. Addition of iron partially reversed the inhibition. The other chelators had low cytotoxic effects that disappeared upon iron saturation. Maltol, particularly in the absence of iron, 1,2-dimethyl-3-hydroxypyrid-4-one and 1-methyl-3-hydroxypyrid-2-one supported DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pathology, Academic Hospital, Uppsala, Sweden.
K
K
Forsbeck
K
K
Nilsson
G J
GJ
Kontoghiorghes
D004247:DNA / Q000096:biosynthesis*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D014168:Transferrin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D007502:Iron Chelating Agents; D014168:Transferrin; D004247:DNA; D007501:Iron