Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system.
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.
Hanslick
Jennifer L
JL
Department of Psychiatry, Washington University, Saint Louis, Missouri 63110-1093, USA.
Lau
Karen
K
Noguchi
Kevin K
KK
Olney
John W
JW
Zorumski
Charles F
CF
Mennerick
Steven
S
Farber
Nuri B
NB
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
D012997:Solvents; D053148:Caspase 3; D004121:Dimethyl Sulfoxide