ABSTRACT
In a concentration providing the maximum in vivo antitumor action, "Bacillus intermedius" RNAase had no in vitro cytotoxic effect on the cells of lympholeukosis NK/Ly. The enzyme did not inhibit the involvement of 3H-thymidine in the DNA biosynthesis in the tumor cells cultivated in vitro. A preliminary in vitro exposure of the cells to the enzyme did not influence their inoculation capacity. It was concluded that the mechanism of the enzyme antitumor action was not associated with the inhibition of the tumor cell viability. It was shown to be due to the activation of the intermediate effector system. The suggested mechanism of the mediated RNAse action on the tumor growth includes stimulation of the host immunity or removal/restriction of the tumor systemic action on the host.
Subject(s)
Antineoplastic Agents/therapeutic use , Bacillus/enzymology , Ribonucleases/therapeutic use , Animals , DNA, Neoplasm/biosynthesis , DNA, Neoplasm/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Lymphoma/drug therapy , Lymphoma/metabolism , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Tumor Cells, CulturedABSTRACT
Cytomorphological changes in the organs of laboratory animals after their treatment with RNAse from Bacillus intermedius were investigated. It was shown that the effect of RNAse on the thymus and spleen was evident from stimulation of the elements of the lympho and hemopoiesis while its effect on the liver manifested itself in increased stromal response of the liver and higher functional activity of the organ. The observed effects did not depend on catalytic activity of the enzyme.
Subject(s)
Bacillus/enzymology , Ribonucleases/pharmacology , Viscera/drug effects , Animals , Hematopoiesis/drug effects , Liver/drug effects , Male , Mice , Spleen/drug effects , Thymus Gland/drug effects , Viscera/cytologyABSTRACT
Cytotoxicity of RNAase from Bacillus intermedius was studied in vitro and in vivo. It was shown that the enzyme had slightly pronounced cytotoxicity according to the tests with inhibition of cell proliferation and biosynthesis of cell nucleic acids. The RNAase was also shown to impair the vital staining by neutral red. The efficiency of the impairment much more depended on the enzyme catalytic activity than on the proliferation and biosynthesis of nucleic acids. In vivo toxicity of RNAase from B. intermedius was 3-5 times higher than that of pancreatic RNAase. Possible mechanisms of the different toxicity of the enzymes are discussed.
Subject(s)
Bacillus/enzymology , Ribonuclease, Pancreatic/toxicity , Ribonucleases/toxicity , Amnion/pathology , Animals , Antineoplastic Agents , Cell Division/drug effects , Culture Media , Dose-Response Relationship, Drug , Female , Humans , In Vitro Techniques , Leukemia, Experimental/pathology , Leukemia, Lymphoid/pathology , Mice , Ovarian Neoplasms/pathology , Ribonuclease, Pancreatic/pharmacology , Ribonucleases/administration & dosage , Ribonucleases/pharmacologyABSTRACT
Identity of the mechanism of antitumour effectiveness of Bac. intermedius and pancreatic RNase and the enzyme independence of the catalytical activity are shown. Differential sensitivity of the implanted tumours of animals to RNase of Bac. intermedius is established.
