In vitro mechanisms of chemopotentiation by tone-burst ultrasound.
We investigated in vitro enhancement of cytotoxicity of chemotherapeutic agents by tone-burst ultrasound. Survival of CHO cell exposed to chemotherapeutic agents in culture medium was determined with and without insonation (1.62 and 0.29 MHz, 10% duty cycle). Insonations up to 0.4 MPa peak pressure (5 kW/m2 spatial and temporal average) occurred in the middle of 1 h drug exposures. Cytotoxicity in ultrasound control groups was never observed. Ultrasound increased the clonogenic cytotoxicity of adriamycin (p = 0.00027 by paired t test) and diaziquone but not of cisplatin or mitomycin C. Potentiation of adriamycin depended on exposure time and tone-burst frequency. .OH production in water occurred at intensities as low as 0.4 kW/m2, but did not increase with added adriamycin. Ultrasound did not affect membrane fluidity, but moderately increased cellular adriamycin accumulation, possibly explaining the observed drug potentiation.
Harrison
G H
GH
Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore 21201, USA.
Balcer-Kubiczek
E K
EK
Gutierrez
P L
PL
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000528:radiation effects*; D001388:Aziridines / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D016466:CHO Cells / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D018929:Cell Culture Techniques; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D006224:Cricetinae; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005434:Flow Cytometry; D017665:Hydroxyl Radical / Q000378:metabolism; D008560:Membrane Fluidity; D016685:Mitomycin / Q000494:pharmacology; D014463:Ultrasonography
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D001388:Aziridines; D016227:Benzoquinones; D017665:Hydroxyl Radical; D016685:Mitomycin; D004317:Doxorubicin; C029108:diaziquone; D002945:Cisplatin