Action of (S)-10-hydroxycamptothecin on P388 leukemia and distribution of the drug in mice.

ABSTRACT

As an inhibitor of the growth of P388 leukemia in mice, (S)-10-hydroxycamptothecin (OPT) was as potent as the parent compound camptothecin (CPT). Incorporation of thymidine into DNA was the parameter most sensitive to OPT in vitro (ED50 approximately 4 micrograms/ml), but incorporation of cytidine into RNA and of acetate into lipids was also reduced significantly in the presence of the drug. The cytofluorometric profile suggested suppression of the S and G2/M phases. The distribution of OPT in mice at 2 and 24 hours after ip injection (10 mg/kg) was essentially similar to that of CPT, with the exception of a somewhat greater concentration of CPT in the liver. In their pharmacology, OPT and CPT appear to be very similar, despite reports that the hydroxy derivative is less toxic.