IRON REVERSES IMPERMEABLE CHELATOR INHIBITION OF DNA-SYNTHESIS IN CCL-39 CELLS

Treatment of Chinese hamster lung fibroblasts (CCl 39 cells) with the impermeable iron(II) chelator bathophenanthroline disulfonate (BPS) in hibits DNA synthesis when cell growth is initiated with growth factors including epidermal growth factor plus insulin, thrombin, or cerulopl asmin, but not with 10% fetal calf serum. The BPS treatment inhibits t ransplasma membrane electron transport. The treatment leads to release of iron from the cells as determined by BPS iron(II) complex formatio n over 90 min. Growth factor stimulation of DNA synthesis and electron transport are restored by addition of di- or trivalent iron to the ce lls in the form of ferric ammonium citrate, ferrous ammonium sulfate, or diferric transferrin. The effect with BPS differs from the inhibiti on of growth by hydroxyurea, which acts on the ribonucleotide reductas e, or diethylenetriaminepentaacetic acid, which is another impermeable chelating agent, in that these agents inhibit growth in 10% fetal cal f serum. The BPS effect is consistent with removal of iron from a site on the cell surface that controls DNA synthesis.