Cisplatin and dimethyl sulfoxide react to form an adducted compound with reduced cytotoxicity and neurotoxicity.
OBJECTIVE
We present work that demonstrates that cisplatin reacts rapidly with dimethyl sulfoxide (DMSO) in solution and identify the structure and reactivity of the resulting compound.


METHODS
Electrospray ionization-mass spectrometry (ESI-MS) and NMR were used to identify the chemical structure of compounds formed when DMSO reacts with cisplatin. We studied the reactivity of the identified compound with DNA. In vitro toxicity studies in neurons and cancer cells and in vivo toxicity studies in rats were used to determine both the cancer chemotherapeutic and toxic effects of the identified compound.


RESULTS
Cisplatin binds rapidly with DMSO to form a DMSO adduct. The resulting compound has reduced ability to bind to double-stranded DNA both in vitro and in cells. This compound has reduced toxicity for cancer cells and neurons in vitro. In vivo nephrotoxicity studies show that the adducted compound has different nephrotoxicity and elimination characteristics than cisplatin.


CONCLUSIONS
From this work, we conclude that dissolving cisplatin in DMSO results in formation of an adducted compound with different therapeutic and biological characteristics. Furthermore, future studies which propose using DMSO in combination with cisplatin for chemotherapeutic treatment in patients must be reconsidered. Due to the rapidity and nature of the reaction, DMSO and cisplatin should not be combined for patient treatment.
Fischer
Stephanie J
SJ
Molecular Neuroscience Program, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905, USA.
Benson
Linda M
LM
Fauq
Abdul
A
Naylor
Stephen
S
Windebank
Anthony J
AJ
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002945:Cisplatin / Q000737:chemistry* / Q000633:toxicity*; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D018736:DNA Adducts / Q000737:chemistry* / Q000633:toxicity*; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000737:chemistry* / Q000633:toxicity*; D005260:Female; D006801:Humans; D007939:Leukemia L1210 / Q000378:metabolism; D013058:Mass Spectrometry; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization
D000970:Antineoplastic Agents; D018736:DNA Adducts; D004277:DNA, Single-Stranded; D012996:Solutions; D004247:DNA; D002945:Cisplatin; D004121:Dimethyl Sulfoxide