Growth promotion of transformed cells by iron in serum-free culture.

The growth of C6 glioma and L1210 leukemic cells has been stimulated in serum-free medium by the addition or iron or transferrin. The growth promoting action of transferrin was lost when iron was chelated in the culture medium using desferrioxamine. L1210 cells can be grown continuously in serum-free medium supplemented with transferrin or FeCl3 only. In this latter case, it has been shown that L1210 cells secrete into the medium some factor which facilitates iron uptake. The growth of L1210 cells in their exponential phase was blocked by desferrioxamine at the G1-S interface of the cell cycle. The action of transferrin on cell growth was also inhibited by propyl gallate - a known antioxidant which prevents lipid peroxidation. The action of iron was more potent than hemin in reversing the influence of propyl gallate on L1210 cell growth. Iron was found to activate purified guanylate cyclase in the presence of unsaturated fatty acids. This suggests that cyclic GMP synthesis could be involved in the promotion of transformed cell growth by iron.