Comparison between 3 H-Daunomycin and its Antimitotic and Antimetabolic Activities in Ascites Sarcoma 180

Abstract

Daunomycin uptake and its antimitotic and antimetabolic activities have been studied in S 180 ascites cells in vivo. The uptake of the tritiated antibiotic was determined by radiochemical methods 15 min and 2 h after the i. p. administration of scalar doses. The inhibiting effects on nucleic acids biosynthesis was evaluated by determining with autoradiographic and radiochemical methods, the incorporation of ³H-thymidine and ³H-uridine 2 h after daunomycin administration. Parallel studies were carried out on the antimitotic activity. The results obtained indicate that daunomycin is already present in the cells 15 min after injection and in proportion to the dose given. Two hours after the injection the level of incorporated radioactivity is lower. Mitotic activity, measured two h after the treatment, is reduced dose proportionally and is completely absent at doses of 2 mg/kg. The incorporation of ³H-thymidine and ³H-uridine is increased in the cells treated with low doses and is reduced only at doses of 2 mg/kg or higher. In these experimental conditions DNA synthesis is reduced to greater extent than RNA synthesis. A comparison of daunomycin uptake and of nucleic acid synthesis inhibition showed a direct proportionality whereas the effect of daunomycin on mitotic activity and on nucleic acids metabolism appear to be dissociated.