Hemoglobin Synthesis inMurineVirus-Induced Leukemic Cells InVitro: Stimulation ofErythroid Differentiation by Dimethyl Sulfoxide

TL;DR: In this paper, the effect of DMSO on leukemic cells was investigated and it was shown that 2% methyl sulfoxide (DMS0) increased the synthesis of hematopoietic cells.

Abstract: Cellsofa clonedlineofmurinevirus- inducederythroleukemia werestimulated todifferentiate alongtheerythroid pathwayby dimethylsulfoxide at concentrations thatdidnotinhibit growth. A riseinthe number ofbenzidine-positive normoblasts was accom- paniedbyincreased synthesis ofheme andhemoglobin andadecrease inthemalignancy ofthecells. Thisaction ofdimethyl sulfoxide, whichwasreversible, may represent thederepression ofleukemic cells topermittheir matura- tion. Theopportunity toexplore thepossibility thatleukemia isa disease resulting fromablock intheprocess ofmaturation of hematopoietic cells hasbeenprovided byestablished tissue culture lines ofmurine virus-induced erythroleukemic cells (1-3). Thesecells, whichgrowinsuspension, havecontinued toexhibit alimited degree ofdifferentiation along theery- throid linethroughout their 4-year serial passage history. Although theysynthesize hemoglobin (4,5),theyaremalig- nantastested bybioassay insyngeneic hosts. Theyproduce virus which, although lowinleukemogenic activity, isahighly effective immunizing agent(6). During thecourseofstudies todetermine theeffect of superinfecting thesecells withFriend leukemia virus, di- methyl sulfoxide (DMS0)wasadded tothemedium. DMS0 hadbeendemonstrated toenhance infectivity ofbothpolio- virus RNA (7)andmengovirus RNA (8), aswell astrans- formation bypolyoma virus (9). Itisalso knowntostabilize enveloped viruses (10). Thewiderange ofbiological activities ofDMSO hasbeendescribed (11). Thepresent report de- scribes aneffect ofDMSO onthedifferentiation ofestablished lines ofmurinevirus-induced leukemic cells andillustrates still another property ofthis compound. Inthedose-response experiments initially setuptodeter- minethetoxicity ofDMSOontheleukemic cell lines, astrik- ingeffect onthedifferentiation ofthese cells wasnoted. Ofthe cells allowed togrowinmediumcontaining 2%DMS0 for4 days, amajority oftheerythroblasts hadmatured tonormo- blasts which stained benzidine-positive