Effects of Anthracyclines on Macromolecules and their Syntheses

Abstract

The cytotoxicity of anthracyclines has been attributed to their ability to inhibit DNA-dependent nucleic acid synthesis by intercalation into DNA (1–3). Exposure of cells in culture to anthracyclines at low concentrations (0.1–10 μM) produces marked inhibition of both DNA and RNA synthesis without appreciable effects on protein synthesis at comparable doses (4–13). In general, preribosomal RNA synthesis is thought to be more sensitive to inhibition by anthracyclines than is total cell RNA synthesis (5, 11–14). These results have led to the grouping of anthracyclines into two mechanistic classes: Class I, those anthracyclines that yield similar IC50 values for inhibition of DNA, total RNA, and nucleolar RNA synthesis ; and Class II, those that are selective for the inhibition of nucleolar RNA synthesis (0.1).