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LDH isoenzyme shifts are frequently observed in several malignant neoplasm when compared with the corresponding normal tissues. In the present work, we studied LDH isoenzyme behaviour both in Yoshida cells and in founder macrophages, before and after polyamine treatment. The choice of polyamine was prompted in that these polycations also act on the enzymatic and metabolic steps. Results obtained evidenced: i) LDH activity was higher in Yoshida cells than in macrophages; ii) polyamine treatment provoked in tumour cells a very strong increase of LDH activity whereas in macrophages only a slight decrease; iii) Yoshida cells showed the presence of 4 LDH isoenzymes only.
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1. Yoshida ascites cells from a strain sensitive to chemotherapy with alkylating agents contained elevated activities of the two enzymes directly responsible for glutathione synthesis, in comparison with a resistant cell strain. The activities of the glutathione-degrading enzyme gamma-glutamyltranspeptidase were comparable in both cell strains. 2. After parenteral administration of chlorambucil to rats carrying either strain of tumour, the activities of the glutathione-synthetic enzymes increased in the sensitive cells, but remained unchanged in the resistant cells. Drug treatment was without effect on the gamma-glutamyltranspeptidase activity of either cell strain. 3. The activities of a number of enzymes concerned in the oxidoreduction of glutathione remained unchanged after the administration of chlorambucil to rats carrying either strain of cells.
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It is shown that L-cystine-bis-(N,N-beta-chloroethyl)-hydrazide-hydro-bromide possesses strong (50-100%) inhibitory effect in vivo against myeloma P-8, carcinosarcoma Walker, lymphosarcoma Pliss, sarcoma Yoshida, sarcoma Jensen and sarcoma 180 in doses 5-12 mg/kg/day. No suppression of the growth of Ehrlich ascites tumor was observed. The acute toxicity (LD50) of this substance on mice and rats is 71 mg/kg and 47 mg/kg respectively.
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