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 with that of mitomycin 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-pulse treatments, and the minimum effective concentrations with and without S9 were 0.625 and 0.0625 micrograms/ml, respectively. The compound increased revertant colonies in Salmonella typhimurium TA102 at the dose range of 10-5000 micrograms/plate with S9. Without S9, FK973 induced a small increase at the dose range of 500-5000 micrograms/plate in two of three independent experiments, but the number of revertant colonies was less than double that of the vehicle control. The compound did not induce any revertant colonies in colonies in S. typhimurium TA100, TA98, TA1535 or TA1537 with or without S9. MMC was confirmed to increase both chromosome aberrations in Don cells and revertant colonies in TA102. The minimum clastogenic and mutagenic concentrations without S9 were 0.0156 microgram/ml and 0.005 microgram/plate, respectively. The results indicate that FK973 needs metabolic activation to induce reverse mutation in prokaryotic cells, but caused chromosome aberrations in mammalian cells without added S9.
Hirai
O
O
Toxicology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Miyamae
Y
Y
Hattori
Y
Y
Takashima
M
M
Miyamoto
A
A
Zaizen
K
K
Mine
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001711:Biotransformation; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D016685:Mitomycin / Q000737:chemistry / Q000633:toxicity; D009152:Mutagenicity Tests; D009154:Mutation; D010078:Oxazines / Q000737:chemistry / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000235:genetics
D000970:Antineoplastic Agents; D010078:Oxazines; C054974:FK 973; D016685:Mitomycin