Molecular modeling: an experimental tool.

The effect of a combination of lithotripter shock waves and cytotoxic drugs was examined in vitro. L1210 cells in suspension were exposed to shock waves during incubation with cisplatin, doxurubicin, daunorubicin, THP-doxorubicin, or aclacinomycin. Proliferation was determined using the 3-4,5 dimethyl-thiazol-2,5 diphenyl tetrazolium bromide assay. Dose enhancement ratios were calculated for each drug in order to determine the effect of the additional exposure to shock waves. In addition, partition coefficients and ICms of the drugs were determined. It was found, that the dose enhancement ratios increased for the drugs with decreasing cytotoxicity. The effect of all five drugs was enhanced by shock waves to a higher degree at 7 min incubation as compared to 50 min incubation. The effect of cisplatin was most significantly enhanced, with a dose enhancement ratio of 6.7 at 7 min incubation. The enhancement increased with the operating voltage used for generating the shock waves, and was only present when cells were exposed to shock waves during the incubation with the drug. An increase in cellular membrane permeability is proposed as the mechanism of interaction between shock waves and drugs. Lithotripter shock waves are pressure pulses of high amplitude and short duration which are used in medicine for the disintegration of urinary and biliary calculi (Chaussy et al., 1980; Sauerbruch et al., 1986). In liver and kidney they can cause haemorrhages, vessel wall damage and venous thrombi The increasing knowledge of the side effects of shock waves in tissues led to investigations of their effect on tumour tissue. Several authors found reduction of tumour volume or even complete remission in small experimental tumours