Abstract: In the present study, we have focused on the specific question of whether ultrasound application (ULS) delivered with optimized parameters for cavitation generation can stimulate apoptosis in lymphoid cell lines. Suspended T and B lymphoid cell lines (Jurkat and Raji, respectively) were exposed to low frequency ULS (750 KHz) at an intensity level of 54.6 W/cm2 spatial peak temporal average (SPTA) at focal area, which was found to be the optimal physical parameter to induce apoptosis in these malignant cell lines. Unsonicated cells and cells exposed to γ‐radiation (20 Gy) using 137Cs source were used as control. Apoptosis was evaluated by cell morphology changes, cell‐cycle analysis, and phosphatidylserine exposure. Fraction of cells with low mitochondria membrane potential was observed 1 h after sonication, accompanied by cytochrome c release from mitochondria to the cytosol and caspase‐3 activation. Here we present evidence that ULS exposure with cavitation formation on malignant lymphoid cell lines differs from γ‐radiation and is associated with time‐dependent apoptosis, which is mitochondria‐caspase dependent.

None of the modalities currently employed to induce apoptosis involves the use of ultrasound energy. We have demonstrated (Cancer Res. 60: 1014, 2000) that selected physical parameters utilized in therapeutic ultrasound (ULS) application resulting in cavitation process induce an apoptotic cell death. The aim of the present study was to investigate ULS application with rational selected physical parameters to optimize ultrasound cavitation- induced cell death and to determine whether apoptosis is involved. High intensity focussed ULS sonication was delivered with an induction of transient cavitation and intensity of 54 W/cm2 to malignant T and B lymphocyte-derived cell lines expressing p53 as Raji, Jurkat and NALM-6 as well as myeloid leukemia cell lines p53 negative HL-60, K562, U937. Here we present evidence that much of the cell damage surviving ULS exposure appears to occur through an apoptotic mechanism. Morphological alterations of apoptotic cells involve nuclear fragmentation and apoptotic body formation. Positive identification of apoptotic cells was based also on the detection of nuclear DNA strand break and changes in the surface of treated cells undergoing apaptosis expressed by the breakup of phosphatidylserine from the inner to the outer side of the membrane layer. In summary, after ULS exposure malignant hemopoietic cell lines can be induced to undergo apoptosis by p53-dependent and p53-independent apoptotic pathways.

The focusing and primary aberration properties of a range of two-cylinder lenses have been determined by trajectory computation. The resistance network analogue was used to obtain the lens fields and the ray equation was integrated numerically by digital computer. Results for the focal lengths, principal plane positions and spherical aberration constants are presented graphically for a large range of geometrical and potential variations.