ABSTRACT
Influence of antiestrogen and antiandrogen derivatives of acylhydrazine, potentiating the antitumoral effect of cytostatics, on properties of nucleoside triphosphatases (NTPases), adenylate content in nuclea of normal and tumoral cells was studied. It was shown that acylhydrazines activated specifically the intranuclear NTPase of normal and tumoral cells. Activity of nuclear membrane-linked NTPases from liver cells was also increased after administration of acylhydrazines, sex hormones or phenobarbital. The increase in activity of intranuclear NTPase (namely ATPase) correlated with decrease of adenylates (ADP, ATP) in nuclea isolated from tumors after simultaneous treatment with acylhydrazines and thiophosphamide. Distinct increase in sensitivity of tumoral cell DNA to the effect of these alkylating preparations appear to be due to noncompensated decrease in content of ATP.
Subject(s)
Adenine Nucleotides/metabolism , Adenosine Triphosphatases/metabolism , Androgen Antagonists/pharmacology , Cell Nucleus/metabolism , Estrogen Antagonists/pharmacology , Hydrazines/pharmacology , Sarcoma 180/metabolism , Animals , Cell Nucleus/drug effects , Female , Kinetics , Liver/metabolism , Male , Mice , Nucleoside-Triphosphatase , Phosphoric Monoester Hydrolases/metabolism , Structure-Activity RelationshipABSTRACT
Hydrazine sulfate significantly potentiated antitumor effect of thiophosphamide in experiments on rats with Walker's tumor. The treatment with hydrazine sulfate (60 mg/kg) plus thiophosphamide (1 mg/kg) resulted in suppression of tumor growth up to 90%, the dosage of thiophosphamide being therapeutically ineffective. Following hydrazine sulfate treatment, the activity (pH: 7.0-7.5-7.75) derived from tumors doubled, as compared with control. Similar results were obtained with enzymatic preparations. The activities of DNP-stimulated ATPase and solubilized enzymes in rat liver were not influenced by treatment.
