Lysis and sonoporation of epidermoid and phagocytic monolayer cells by diagnostic ultrasound activation of contrast agent gas bodies.

Epidermoid A431 (human carcinoma) and phagocytic RAW-264.7 cells were grown as monolayers on 5-microm thick Mylar sheets by standard culture methods. The sheets formed one window of disk-shaped ultrasound (US) exposure chambers. A diagnostic US machine in spectral Doppler mode was used for exposure with a 3.5-MHz scanhead aimed upward at the chamber in a 37 degrees C water bath. Sonoporation and cell lysis were evaluated for assessment of cell membrane damage. For both epidermoid and RAW cells on the upper window with 1% Optison contrast agent, cell lysis was detectable in addition to sonoporation. The phagocytic cells tended to retain the gas bodies when incubated with contrast agent, and membrane damage occurred even for exposure on the bottom window. The effects were also seen for RAW cells incubated with 5% contrast agent for 15 min and then rinsed before exposure. Above a threshold range for lysis and sonoporation of 0.09 to 0.23 MPa, the counts of affected cells increased for both cell lines to about 20% at 0.83 MPa. These results indicate relatively low thresholds for membrane damage induced by diagnostic US activation of contrast agent gas bodies, with a potential for targeting of these effects to phagocytic cells.