Effects of different transferrin forms on transferrin receptor expression, iron uptake, and cellular proliferation of human leukemic HL60 cells. Mechanisms responsible for the specific cytotoxicity of transferrin-gallium

Journal Article · Mon Dec 01 00:00:00 EST 1986 · J. Clin. Invest.; (United States)

DOI:https://doi.org/10.1172/JCI112746· OSTI ID:6927218

Chitambar, C R; Seligman, P A

We have previously shown that human leukemic cells proliferate normally in serum-free media containing various transferrin forms, but the addition of transferrin-gallium leads to inhibition of cellular proliferation. Because gallium has therapeutic potential, the effects of transferrin-gallium on leukemic cell proliferation, transferrin receptor expression, and cellular iron utilization were studied. The cytotoxicity of gallium is considerably enhanced by its binding to transferrin and cytotoxicity can be reversed by transferrin-iron but not by other transferrin forms. Exposure to transferrin-gallium leads to a marked increase in cell surface transferrin binding sites, but despite this, cellular /sup 59/Fe incorporation is inappropriately low. Although shunting of transferrin-gallium to another cellular compartment has not been ruled out, other studies suggest that transferrin-gallium impairs intracellular release of /sup 59/Fe from transferrin by interfering with processes responsible for intracellular acidification. These studies, taken together, demonstrate that inhibition of cellular iron incorporation by transferrin-gallium is a prerequisite for inhibition of cellular proliferation.

• Research Organization: Medical College of Wisconsin, Milwaukee
• OSTI ID: 6927218
• Journal Information: J. Clin. Invest.; (United States), Vol. 6
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CELL PROLIFERATION
INHIBITION
GALLIUM
RECEPTORS
TOXICITY
TRANSFERRIN
CELL DIVISION
COPPER
FERRITIN
IRON 59
LEUKEMIA
TUMOR CELLS
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
COMPLEXES
DAYS LIVING RADIOISOTOPES
DISEASES
ELEMENTS
EVEN-ODD NUCLEI
GLOBULINS
GLOBULINS-BETA
HEMIC DISEASES
INTERMEDIATE MASS NUCLEI
IRON COMPLEXES
IRON ISOTOPES
ISOTOPES
MEMBRANE PROTEINS
METALLOPROTEINS
METALS
NEOPLASMS
NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
TRANSITION ELEMENT COMPLEXES
TRANSITION ELEMENTS
560300* - Chemicals Metabolism & Toxicology