Recently there has been renewed interest in the use of ultrasound for cancer therapy since the combination of ultrasound and hematoporphyrin, a photochemical sensitizer for tumor treatment in photodynamic therapy, showed marked synergistic effects on the inhibition of tumor growth. Sonosensitization, a term that can be used to describe the potentiation of drug toxicity by ultrasound, was also found for adriamycin, daunomycin, diaziquone, and also for organic solvents dimethylsulfoxide, and N, N- dimethylformamide (DMF). Currently, the underlying mechanisms of the synergistic effects of drugs and ultrasound on cell killing are not understood and need further investigations. The understanding of the mechanism of drug/ultrasound synergism is essential for possible further therapeutic applications of sonosensitizing therapy in tumor treatment. Electron spin resonance and spin trapping methods were used to investigate the sonochemistry of DMF/water mixtures using the spin trap 3,5-dibromo-4- nitrosobenzene sulfonate (DBNBS). The methyl and H2CN(CH3)C(O)H radicals were spin trapped with DBNBS in aqueous DMF mixtures exposed to 5OkHz ultrasound under argon. The yields of these radical adducts increase with increasing molar fraction of DMF. This behavior is different from the previously investigated aqueous mixtures of organic solvents with vapor pressures higher than water, which results in dampening of the cavitation events due to the effect of =Cp/Cv. In addition to the radicals spin trapped in queous DMF mixtures the N(CH3)R radical were detected using the spin trap nitrosodurene (ND) in sonolysis of pure DMF. The kinetic isotope effect, kH/kD, for the ultrasound-induced production of 'CHRR' and 'CDRR' radicals in mixtures of n-dodecane/n-dodecane-d26 and toluene/toluene-d8 was used to probe the temperatures of various sonochemical reaction regions: the temperature of the region of hydrogen abstraction radical formation ('CHRR') in n-dodecane was estimated to be 75O+/- 150 K; the effective temperature of the region where benzyl radicals are formed from toluene by sonochemical pyrolysis was estimated to be about 6000K. This method appears to be a promising tool for probing the temperatures of different sonochemical regions and mechanisms of the processes involved in sonodynamic interactions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CM006358-11
Application #
3752332
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Division of Cancer Treatment
Department
Type
DUNS #
City
State
Country
United States
Zip Code