title: Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system.
abstract: Dimethyl sulfoxide (DMSO) is a solvent that is routinely used as a cryopreservative in allogous bone marrow and organ transplantation. We exposed C57Bl/6 mice of varying postnatal ages (P0-P30) to DMSO in order to study whether DMSO could produce apoptotic degeneration in the developing CNS. DMSO produced widespread apoptosis in the developing mouse brain at all ages tested. Damage was greatest at P7. Significant elevations above the background rate of apoptosis occurred at the lowest dose tested, 0.3 ml/kg. In an in vitro rat hippocampal culture preparation, DMSO produced neuronal loss at concentrations of 0.5% and 1.0%. The ability of DMSO to damage neurons in dissociated cultures indicates that the toxicity likely results from a direct cellular effect. Because children, who undergo bone marrow transplantation, are routinely exposed to DMSO at doses higher than 0.3 ml/kg, there is concern that DMSO might be producing similar damage in human children.
authors.affiliation: Department of Psychiatry, Washington University, Saint Louis, Missouri 63110-1093, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hanslick
authors.forename: Karen
authors.initials: K
authors.lastname: Lau
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Noguchi
authors.forename: John W
authors.initials: JW
authors.lastname: Olney
authors.forename: Charles F
authors.initials: CF
authors.lastname: Zorumski
authors.forename: Steven
authors.initials: S
authors.lastname: Mennerick
authors.forename: Nuri B
authors.initials: NB
authors.lastname: Farber
mesh_terms: D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000648:ultrastructure; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000633:toxicity
chemical_list: D012997:Solvents; D053148:Caspase 3; D004121:Dimethyl Sulfoxide