Nonhaem complexes of FeIII stimulate cell attachment and growth by a mechanism different from that of serum, 2-oxocarboxylates, and haemproteins.

Most cell lines, even those producing their own growth factors, need a serum supplement when growing in several commonly used media. The requirement for serum to sustain attachment and growth in RPMI 1640 and MEM has been found to be met by a range of 2-oxocarboxylates, by diverse coordination complexes of FeIII, and by a variety of haem-containing proteins including catalase. The latter directly implicates H2O2 in the serum shift-down effects. H2O2 was found to accumulate in low serum media under normal laboratory lighting conditions to levels that were shown to be sufficient, when added to freshly prepared media, to explain the depressed cell performance. With the exception of some of the nonhaem FeIII coordination complexes, substances found to stimulate cell attachment and growth were capable of scavenging H2O2. This suggests that an important function of serum and the 2-oxocarboxylates (alpha-keto acids) frequently used as "nonessential" medium additives is to remove H2O2 produced photodynamically during the storage and manipulation of media containing a high content of riboflavin. However, the nonhaem FeIII complexes with saturated coordination shells, although capable of reducing photodynamic generation of H2O2 to a greater or lesser extent, have their prime effect by an unknown, intriguing mechanism, probably based on a common redox function.