Rational Chemotherapy: Inhibition of Polymerase Activity of Cancer Cells

Abstract

To the Editor.— Recent data indicate that transformation of normal cells by tumor viruses appears to require altered DNA polymerase activity to transcribe new genetic information. Multiple workers have noted the promise for rational cancer chemotherapy of drugs depressing RNA-dependent DNA polymerase (reverse transcriptase) activity from tumor viruses and human acute leukemia cells. The drugs include rifamycin antibiotics (J Natl Cancer Inst49:761, 1972) and clinically promising sulfhydryl (SH)-inhibitors (Knock et al inOncology, Nov, 1972). At concentrations as low as 10μg/ml, clinically useful SH-inhibitors depress reverse transcriptase activity of human leukemic lymphocytes to 12% to 16% of control, activity usually far exceeding that of available rifamycins. The SH-inhibitors were selected by performing three in vitro sensitivity tests on hundreds of human cancers: namely agar plate assay, the Kondo sensitivity test, and radioactive tracer studies monitoring the incorporation of labeled precursors to DNA, RNA, and protein of tumors. The three