In Vitro Biological Activity of Adriamycin

Abstract

Adriamycin is an antibiotic, isolated from cultures of a mutant of Streptomyces peucetius, var. caesius, with a chemical structure very similar to daunomycin but with a higher therapeutic index in experimental tumors. The biological activity of this antibiotic has been studied in vitro on the HeLa cell strain. Adriamycin quickly penetrates into the cells and fixes to the nuclear structures with a marked localization at the level of the perinucleolar chromatin. It causes a marked and immediate disturbance of the mitotic process, viz. pre-prophasic inhibition at the low doses and mitotic block at the higher doses. Even the synthesis of DNA and RNA, evaluated autoradiographically as incorporation of ³H-thymidine and ³H-uridine, appear markedly inhibited. The viability of the cells, tested both as regards capacity to give rise to colonies and as regards proliferative activity of a cell population, was seriously reduced, in a degree proportional to the period of treatment and to the concentration of the antibiotic, until total inhibition. In comparison with daunomycin, adriamycin exerts an immediate antimitotic and anti-metabolic effect which, at equivalent doses, is slightly lower than that of daunomycin. The long-term antiproliferative activity on cellular proliferation is however, identical for the two antibiotics.