Selective Interruption of High Molecular Weight RNA Synthesis in HeLa Cells by Camptothecin

Abstract

THE study of macromolecular metabolism in eukaryotic cells has depended to a large extent on the use of selective inhibitors. Camptothecin is a potent, rapidly acting inhibitor of both DNA and RNA synthesis^1–3 which first came to attention as a potential anti-tumour agent⁴, and which has since been shown to have the remarkable property of inducing breaks in cellular DNA⁵; it also has unusual effects on RNA synthesis possibly as a result of DNA breakage. We show that the drug causes aberrant synthesis of high molecular weight nuclear RNA, but has a much smaller effect on the labelling of 4S RNA and does not affect 5S RNA synthesis. If the effect on RNA synthesis is due to DNA breakage, the results suggest that the breaks are induced at specific points.