Genotoxicity Tests on Hyrubicin ID6105, a Novel Anthracycline Anticancer Agent

The genotoxic potential of Hyrubicin lD6105, a novel anthracycline anticancer agent, was examined on bacterial mutagenicity, mammalian cell chromosome aberration and mouse micronucleus tests. In mutagenicity (Ames') test, Salmonella typhimurium strain TA98, TA100, TA1535 and TA1537, and Escherichia coli WP2uvrA- were treated with ID6105 at doses of 312.5, 625, 1,250, 2,500 and 5,000 $\mu\textrm{g}$/ plate with or without a metabolic activation system (S9 mix). Interestingly, ID6105 significantly enhanced the number of revertant colonies of TA98 strain at all dose levels used, in the presence or absence of S9 mix, without affecting other strains of S. typhimurium and E. coli. In chromosome aberration test using cultured chinese hamster lung fibroblasts, ID6105 (1.25, 2.5 and 5 $\mu\textrm{g}$/ml) did not increase the number of aberrant cells, compared with vehicle control. in the presence or absence of S9 mix. In addition, ID6105 treatment (2.5, 5 and 10 mg/kg) did not induce micronucleated polychromatic erythrocytes in mice. Taken together, it is suggested that ID6105 might not affect chromosome integrity in mammalian system in vitro and in vivo, although it may induce frame shift mutation of specific bacterial strain such os S. typhimurium TA98.

새로운 Anthracycline계 항암제 Hyrubicin ID6105에 대한 유전독성연구