A new antitumor antibiotic, FR-900482: V. Interstrand DNA-DNA cross-links in L1210 cells.

FR-900482 (Fig. 1) is a new antitumor antibiotic isolated from the culture broth of Streptomyces sandaensis No. 68971~3). It has potent cytotoxic effects against murine and human tumor cells2>4), and weak myelosuppressive effects in mice5). The mechanisms by which FR-900482 induces cytotoxic effects have not been defined. Some antitumor drugs induce interstrand DNA-DNA cross-links or DNA strand breaks in cells6>7). In this paper we describe the effects of FR-900482 on macromolecular syntheses in cultured murine L1210 leukemia cells and the interaction of the compound with DNAin the cells and plasmids. First, cell growth and macromolecular syntheses were examined in LI210 cells exposed to FR-900482. The cells were grown in suspension in Dulbecco's modified Eagle's mediumsupplemented with 10%fetal bovine serum in culture flasks in 5% CO2-95% air atmosphere. In one experiment the cells (1 x106) were incubated with FR-900482 for 48 hours at 37°C, and in another incubated for 1 hour, washed twice with cold phosphate-buffered saline (PBS)