A microtitre cytotoxicity assay useful for the discovery of fermentation-derived antitumor agents

A microtiter cytoxicity assay using mammalian cell lines was developed to detect fermentation-derived antitumor agents. Two murine (AKR, B16) and four human (HTB-31, KB, MOSER, RCA) cell lines were used to evaluate 2000 fermentation broth supernatants. The mammalian cell lines tested showed different spectra for fermentation broth activity, as predicted by responses to known antitumor agents. Data were compared with standard antimicrobial assays historically used to screen for antitumor activity for this set of 2000 broths. There was an overlap of approximately 30% of broths identified as containing in vitro bioactivity by the two assay systems. Sixty-three antimicrobially active broths were tested for activity in P388 in vivo; the cytotoxicity assay predictive rate (40%) was twice that of the antimicrobial assays.