Persulfide sulfur is a growth factor for cells defective in sulfur metabolism

Several systems which generate persulfide sulfur promote in vitro proliferation of L1210 murine lymphoma cells. The systems include cysteine disulfides and pyridoxal, cystamine and diamine oxidase, beta-mercaptoalcohol disulfides and an alcohol dehydrogenase, and sulfide-treated proteins and a thiol. Persulfide sulfur is very unstable at pH near 7 and an essential feature of the growth-supporting systems is the ability to generate persulfide sulfur at a very low rate for long periods of time. Methyl disulfides (R--S--S--CH3) also support growth of L1210 cells and are more stable than persulfides (R--S--S--H). The requirement for these sulfur groups by L1210 cells may be related to the fact that these cells are defective in at least two enzymes of sulfur metabolism, cystathionase and 5'-methylthioadenosine phosphorylase. These findings provide the first evidence that persulfide sulfur may have a physiological role.