The relationship between sister chromatid exchange induction and leukemogenicity of different cytostatics

The genotoxicity of frequently used cytostatic agents was characterized by the enumeration of the sister chromatid exchanges (SCEs) induced by them in vivo in phytohemagglutinin-stimulated peripheral blood lymphocytes. Fifty-nine cancer patients undergoing and off chemotherapy are included in this study. The aim was to identify cytostatics according to their ability to alter the SCE frequency. Cytostatics with strong SCE-inducing ability (melphalan, cyclophosphamide, cyclophosphamide + vincristine + 5-fluorouracil, cyclophosphamide + vincristine + procarbazid + prednisolone) usually exhibited a longlasting SCE elevation. Cytosine arabinoside, hydroxyurea, vincristine, 5-fluorouracil, tamoxifen, and azathioprine did not induce SCEs. These data were compared with the leukemogenic potential of the same drugs in order to validate the relevance of SCE studies in man to signal carcinogenic hazards. It was found that over 80% of all secondary leukemias (collected from the world literature from 1930 to 1980) were preceded by the administration of cytotoxic compounds inducing long-lasting SCE elevation in lymphocytes. Only 3% of all secondary leukemias can be attributed to drugs not inducing SCEs in vivo in PHA-stimulated lymphocytes. This indicates that the lesions important for SCEs and secondary leukemias to emerge bear close biological similarities. Thus SCE studies can be used in selecting therapeutical protocols or new cytostatics with less carcinogenic potential to man.     

The Effect of Tunicamycin on Target Cell Susceptibility to Natural Killer Cell Cytotoxicity

Several sets of data indicate the possibility that carbohydrate moieties on the target cell are important structures in natural killer (NK) cell-mediated lysis. Striking changes in the NK susceptibility of targets can be induced in several systems involving in vitro differentiation of tumour cell lines. The effect on target cells of the glycosylation inhibitor tunicamycin, which acts by blocking the dolichol-dependent asparagine-linked glycosylation pathway was investigated. Using several different tumour cell lines we can conclude that: asparagine-linked carbohydrate chains do not contribute directly to NK susceptibility, induced differentiation may or may not be linked with a change in NK susceptibility, and secondary changes caused by tunicamycin treatment may lead to alterations in the gangliosides, a finding that is positively correlated with decreased NK susceptibility.     

Stimulation of glycolysis in Ehrlich ascites carcinoma cells with phenylhydrazonopropanedinitrile and others uncouplers of oxidative phosphorylation

The metabolic consequences of the uncoupling effect of phenylhydrazonopropanedinitrile and others uncouplers of oxidative phosphorylation on Ehrlich ascites carcinoma (EAC) cells were investigated. Upon application of uncouplers in concentrations stimulating the respiration of EAC cells the accelerate glucose uptake and lactate production was observed. The maximal glycolysis stimulation was fourfold in relation to control at the given experimental conditions. Simultaneously the degree of conversion of glucose on lactate was increased. The acceleration of glycolysis was accompanied by stimulation of 14C-labeled adenine and valine incorporation indicating the increased rate of biosynthetic processes. The prolongation of uncoupler action time and application of their higher concentrations cause the inhibition of glycolysis and biosynthetic processes which is evoked with nonspecific effects of the compounds.     

Effect of transtympanally applied lidocaine on the cochleovestibular function

Twenty-two patients with recurring attacks of tinnitus, hearing loss and dizziness were treated with transtympanally injected lidocaine. The tinnitus improved in 19, and the pure tone and speech audiometric thresholds decreased in 15 cases. The dizziness and latent spontaneous nystagmus disappeared in all subjects where these symptoms were manifest before treatment.