Effect of FK973, a new antitumor antibiotic, on the cell cycle of L1210 cells in vitro.

Our previous study showed that FK973 (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1,11- diazatetracyclo[7.4.1.0(2,7)0(10,12)]tetradeca-2,4,6-trien-6 ,9-diyl diacetate), a novel substituted dihydrobenzoxazine, which is a derivative of the fermentation product of Streptomyces sandaensis No. 6897, had strong antitumor effects on experimental tumors in vitro and in vivo. In this report, we investigated its effect on the cell cycle of murine leukemia L1210 cells in vitro by means of DNA/5-bromo-2'-deoxyuridine double staining and compared these effects with those of other antitumor drugs. Both FK973 and mitomycin C arrested the cells in the G2 phase. Vinblastine arrested the cells in the M phase and cytosine arabinoside, in the G1 phase. Although FK973 and mitomycin C were shown to act on the cell cycle in a similar way, FK973 was slower in producing its effect. From the results, FK973 arrests the cells in the G2 phase, and it appears that FK973 must be converted into the activated form in the cells for the development of its antitumor effects.