MICROBIAL MUTAGENICITY AND IN-VITRO CHROMOSOME ABERRATION INDUCTION BY FK973, A NEW ANTITUMOR AGENT

The genotoxic activity of a new antitumor agent, FK973, was compared w ith that of mitomucin C (MMC) in eukaryotic and prokaryotic cells. In chromosome aberration tests using Chinese hamster fibroblast Don cells , FK973 induced a dose-related increase of aberrant cells after 6 h-pu lse treatments, and the minimum effective concentrations with and with out 89 were 0.625 and 0.0625 mu g/ml, respectively. The compound incre ased revertant colonies in Salmonella typhimurium TA102 at the dose ra nge of 10-5000 mu g/plate with S9. Without 89, FK973 induced a small i ncrease at the dose range of 500-5000 mu g/plate in two of three indep endent experiments, but the number of revertant colonies was less than double that of the vehicle control. The compound did not induce any r evertant colonies in S. typhimurium TA100, TA98, TA1535 or TA1537 with or without S9. MMC was confirmed to increase bath chromosome aberrati ons in Don cells and revertant colonies in TA102. The minimum clastoge nic and mutagenic concentrations without S9 were 0.0156 mu g/ml and 0. 005 mu g/plate, respectively. The results indicate that FK973 needs me tabolic activation to induce reverse mutation in prokaryotic cells, bu t caused chromosome aberrations in mammalian cells without added S9.