Iron chelators of different physicochemical properties were studied for their ability to donate iron in vitro to uninduced K562 cells, human bone marrow cells and purified human erythroblasts. To a large extent uptake was found to be related to lipophilicity and those chelators able to deliver iron to the cells in significant amounts were also able to deliver iron to ferritin and haem. Some differences in the distribution of iron delivered was observed but no chelator showed exclusive delivery to or rejection of a particular cellular iron compartment. Several chelators could probably substitute for transferrin and be used to probe metabolic events subsequent to iron removal from transferrin. Two chelators which were excellent iron donors were also found to cause considerable inhibition of iron incorporation into haem from transferrin. The implications of this for in vivo toxicity are briefly discussed.
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Ali FMK, May A, McLaren GD, Jacobs AJ (1982) A two step procedure for obtaining normal peripheral blood T-lymphocytes using continuous equilibrium density. J Immunol Methods 49:185–191
Barnekow A, Winkelman G (1978) Use of iron from transferrin and microbial chelates as substrate for heme synthetase in transform and primary erythroid cell cultures. Biochim Biophys Acta 543:530–535
Bottomley SS, Wolfe LC, Bridges KR (1985) Iron metabolism in K562 erythroleukemic cells. J Biol Chem 260:6811–6815
Cavill I (1971) The preparation of59Fe-labelled transferrin for ferrokinetic studies. J Clin Pathol 24:472–474
Forsbeck K, Nillson K, Kontoghiorghes GJ (1987) Variation in iron accumulation, transferrin membrane binding and DNA synthesis in the K562 and U937 cell lines induced by chelators and their complexes. Eur J Haematol 39:318–325
Hemmaplardh D, Morgan EH (1974) The mechanism of iron exchange between synthetic iron chelators and rabbit reticulocytes. Biochim Biophys Acta 373:84–99
Hodgetts J (1984) A study of human erythroid bone marrow cells and their iron metabolism. MSc Thesis, University of Wales
Hoy T, Humphreys J, Jacobs A, Williams A, Ponka A (1979) Effective iron chelation following oral administration of an isoniazid-pyridoxal hydrazone. Br J Haematol 43:443–449
Kontoghiorghes GJ (1982) The design of orally active iron chelators for the treatment of thalassaemia. PhD Thesis, University of Essex. British Library Microfilm D66194/86
Kontoghiorghes GJ (1986) Orally active α-ketohydroxypyridine chelators: studies in mice. Mol Pharmacol 30:670–673
Kontoghiorghes GJ (1987a) Iron chelation in biochemistry and medicine. In: Rice-Evans C (ed) Free radicals, oxidant stress and drug action. Richelieu Press, London, pp 277–303
Kontoghiorghes GJ (1987b) Orally active α-ketohydroxypyridine iron chelators: effects on iron and other metal mobilisation. Acta Haematol 78:212–216
Kontoghiorghes GJ (1988) Structure/red blood cell permeability activity of iron(III) chelator complexes. Inorg Chim Acta 151:101–106
Kontoghiorghes GJ (1990) Chelators affecting iron absorption in mice. Arzneim-Forsch (in press)
Kontoghiorghes GJ, Sheppard L (1987) Simple synthesis of the potent iron chelators 1-alkyl-3-hydroxy-2-methylpyrid-4-ones. Inorg Chim Acta 136: L1 1-L12
Kontoghiorghes GJ, Piga A, Hoffbrand AV (1986) Cytotoxic and DNA inhibitory effects of iron chelators on human leukaemic cell lines. Haematol Oncol 4:195–204
Kontoghiorghes GJ, Aldouri M, Sheppard L, Hoffbrand AV (1987a) 1,2-dimethyl-3-hydroxypyrid-4-one. An orally active chelator for the treatment of iron overload. Lancet 1:1294–1295
Kontoghiorghes GJ, Aldouri MA, Hoffbrand AV, Barr J, Wonke B, Kourouclaris T, Sheppard L (1987b) Effective chelation of iron inβ-thalassaemia with the oral iron chelator 1,2-dimethyl3-hydroxypyrid-4-one. Br Med J 295:1509–1512
Landschulz W, Thesleff I, Ekblom P (1984) A lipophilic iron chelator can replace transferrin as a stimulator of cell proliferation and differentiation. J Cell Biol 98:596–601
Lawson AAH, Owen ET, Mowat AG (1967) Nature of anaemia in rheumatoid arthritis. VII. Storage of iron in rheumatoid disease. Ann Rheum Dis 26:552–559
May A, DeSouza P, Barnes K, Jacobs A (1982) Erythroblast iron metabolism in sideroblastic marrows. Br J Haematol 52:611–621
Ponka P, Borova J, Neuwrit J, Fuchs O, Necas E (1979) A study of intracellular iron metabolism using pyridoxal isonicotinoyl hydrazone and other iron-chelating agents. Biochim Biophys Acta 586:278–297
Ponka P, Schulman HM (1985) Acquisition of iron from transferrin regulates reticulocyte heme synthesis. J Biol Chem 260:14717–14721
Vrengdenhil G, Swaak AJG, Kontoghiorghes GJ, Van Eijk HG (1989) Efficasy and safety of oral iron chelator L1 in Anaemic rheumatoid arthritis patients. Lancet II 1398–1399
Yamamoto RS, Williams GM, Frankel HH, Weisburger JH (1971) 8-Hydroxyquinoline: chronic toxicity and inhibitory effects on the carcinogenicity ofN-2-fluorenylacetamide. Toxicol Appl Pharmacol 19:687–698
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Kontoghiorghes, G.J., May, A. Uptake and intracellular distribution of iron from transferrin and chelators in erythroid cells. Biol Metals 3, 183–187 (1990). https://doi.org/10.1007/BF01140577
- Erythroid cells
- Iron uptake
- Oral chelators