Effects of sulfhydryl compounds on Friend virus-infected spleen cells in vitro.

Primary cultures of Friend virus-infected spleen cells have a marked increase of hemoglobin synthesis in vitro in the absence of added erythropoietin. Seven sulfhydryl compounds were tested in this liquid culture system and all were found to enhance hemoglobin synthesis in a dose-dependent fashion. An optimum concentration for each compound was determined beyond which inhibition was observed. The most effective compounds were found to be cysteine and glutathione. Addition of the compounds during the early times after culture initiation has the greatest effect. Although they exhibited different dose-response curves, the oxidized counterparts of two SH compounds were also effective. An inverse relationship between the optimum concentration of cysteine and the density at which the Friend virus-infected cells were seeded was noted. The SH effects were not specific for virus-infected cells since some of these compounds also enhanced erythropoietin-induced hemoglobin synthesis in mouse bone marrow and spleen cell cultures. Whereas cysteine and glutathione were most effective in enhancing Friend virus-induced hemoglobin synthesis, thioglycerol was most active in enhancing the response to erythropoietin. Uninfected cultures of marrow or spleen cells, incubated without erythropoietin, failed to increase their hemoglobin synthesis upon inclusion of SH compounds in the growth medium. An enhancement of the virus-induced hemoglobin synthesis occurred after 72 h of cell culture, while for erythropoietin-induced hemoglobin synthesis it occurred after 24 and 48 h. It appears that the SH compounds do not directly increase hemoglobin synthesis, but greatly facilitate an ongoing stimulation by Friend virus or erythropoietin.