IRON AT THE CELL-SURFACE CONTROLS DNA-SYNTHESIS IN CCL-39 CELLS

Treatment of CCI 39 cells with the impermeable iron II chelator bathop henanthroline disulfonate (BPS) inhibits both DNA synthesis and transp lasma membrane electron transport. The inhibition persists when the BP S is removed, and the extract from 10(6) cells contains up to 1.28 nmo les iron II chelated to BPS. The BPS iron II chelate itself is not inh ibitory. Both DNA synthesis and electron transport are restored by add ition of mu M iron II or iron III compounds to extracted cells. Other impermeable chelators for iron II give similar inhibition, whereas the iron III-specific Tiron or copper-specific bathocuproine sulfonate do not inhibit. The inhibition differs from the permeable iron III chela tor inhibition of ribonucleotide reductase, because inhibition of DNA synthesis by the permeable chelators is reversed when chelator is remo ved. The response to growth factors also differs, with no impermeable chelator inhibition on 10% fetal calf serum contrasting to inhibition by permeable chelators. DNA synthesis with both activation of tyrosine kinase with EGF plus insulin or by thrombin or ceruloplasmin led to p rotein kinase C activation as inhibited by It is proposed that an iron available on the cell the impermeable chelators. surface is required for DNA synthesis and plasma membrane electron transport. (C) 1994 Aca demic Press, Inc.