Summary.-Ehrlich ascites tumours (EAT) were grown in mice by injecting 1 x 106 cells intraperitoneally. In mice which received one or more injections of 30 mg soybean trypsin inhibitor (TI) i.p. during tumour growth, the number of recoverable tumour cells was significantly reduced by up to 92%. Also, the mean size of these cells was significantly smaller.When the rate of labelled thymidine incorporation in vitro was compared in TItreated and control cells, no significant differences were detected. However, when the population doubling time of EAT cells in vivo was calculated, it was apparent that recoverable TI-treated cells were dividing more rapidly than controls. Consequently, the reduced number of cells recovered from TI-treated mice did not result from a reduced growth rate.Viability, assessed by trypan blue dye exclusion and rate of labelled chromium release, was the same in TI-treated and control cell populations. Thus TI was nontoxic to EAT cells and the reduced number of cells from treated tumours was not therefore due to cytotoxicity.Scanning electron microscopy revealed that normal EAT cells did not adhere to internal host surfaces but that after TI treatment they adhered in lar e numbers to produce an appearance which resembled a confluent monolayer. This binding to host tissue accounted for the reduction in the number of cells recovered from TItreated animals. We propose that TI acts as a protease inhibitor to prevent intrinsic proteolytic enzyme activity at the tumour cell surface. This activity would normally destroy the binding sites required for adhesion to host tissue.
1. Azumolene sodium is a new water-soluble derivative of dantrolene sodium that also acts as a skeletal-muscle relaxant. 2. Azumolene (6 mumol/L) inhibited the hypercontractility induced separately by 3% halothane, 2 mmol/L caffeine and 80 mmol/L potassium chloride in isolated malignant hyperpyrexia (MH)-susceptible muscle. Azumolene was equipotent with dantrolene in inhibiting the abnormal responses. 3. Like dantrolene, azumolene (6 mumol/L) not only prevented but reversed the abnormal contractures induced by halothane and caffeine. Contracture responses to caffeine were also modified by azumolene in control preparations. 4. In the presence of maximal effective concentrations of dantrolene, azumolene failed to further relax caffeine-induced contractures, and the converse was also true. This was observed in both MH-susceptible and control preparations. 5. Sarcoplasmic reticulum Ca(2+)-dependent ATPase activity from MH-susceptible and control muscle was not affected by azumolene. 6. Like dantrolene, azumolene may inhibit Ca2+ release directly from the sarcoplasmic reticulum and be of therapeutic value for the treatment of MH.
B.A.C.R. 14TH ANNUAL GENERAL MEETING has been the successful collection of large numbers of mitotic cells over a 3-4 hour period using a constant gentle washing procedure for large monolayers. The arrested cells show almost perfect metaphase synchrony and pass out of mitosis synchronously with similar kinetics to isotonically collected mitoses.
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