‘Water Structure’ versus ‘Radical Scavenger’ theories as explanations for the suppressive effects of DMSO and related compounds on radiation-induced transformation in vitro

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Abstract
We report here that dimethylsulfoxide (DMSO): (i) suppresses radiation-induced transformation in vitro, even when DMSO treatments begin as late as 10 days post-irradiation (when cells are in the confluent, stationary phase of growth); (ii) inhibits the 12-O-tetradecanoylphorbol-13-acetate (TPA) enhancement of radiation-induced transformation in vitro; (iii) does not affect the expression of transformed cells as foci (when surrounded by non-transformed cells); and (iv) may be affecting radiation-induced transformation through its solvent properties (i.e. the ‘Water Structure’ theory), while its effects on the TPA enhancement of radiation transformation may be mediated by its free radical scavenging abilities. DMSO, dimethylformamide (DMF) and dimethylacetamide (DMA) are similar solvents which are all very effective in their ability to suppress radiation-induced transformation in vitro (at concentrations in the cellular media down to 0.01%). As DMSO is known to be an extremely effective OH free-radical scavenging agent, while DMF and DMA are not as efficient at scavenging free radicals, our results suggest that properties other than free-radical scavenging ability may be important in the suppressive effects of these compounds on radiation-induced transformation in vitro. It is known that low concentrations of such basic aprotic solvents modify water structure so as to suppress the protic (H-bond donor) reactivity of water and enhance its basic (H-bond receptor) reactivity. These reactivity changes may well be responsible for the effects noted above. DMSO, DMF and DMA are also capable of suppressing the TPA enhancement of radiation transformation (at concentrations of the compounds of 0.1% or higher). For this effect, the ability of these compounds to scavenge OH shows a general correlation with their ability to suppress the TPA enhancement of transformation, suggesting that the ‘Radical Scavenger’ theory may explain the ability of DMSO to suppress promotion in vitro.