Genotoxicity Study of sophoricoside derivatives in mammalian cells system

To develope the novel anti-allergic drug, many sophoricoside derivatives were synthesized. Among these derivatives, JSH-II-3, JSH-Ⅵ-3, JSH-Ⅶ-3, and JSH-Ⅷ-3 were selected and subjected to high throughput toxicity screening (HTTS) because they revealed strong IL-5 inhibitory activity and limitation of quantity. Mouse lymphoma thymidine kinase (tk$\^$+/-/) gene assay (MOLY) and single cell gel electrophoresis (Comet) assay in mammalian cells were used as HTTS tool in our laboratory. In MOLY assay, JSH-Ⅶ-3 at 50 ∼ 6 $\mu\textrm{g}$/ml concentrations was not shown significant mutagenic effect in the absence and presence of S-9 metabolic activation system. However, the concentration of ISH-II-3, 38 $\mu\textrm{g}$/ml, induced increased mutation frequency (MF) in the presence of S-9 metabolic activation system. Also in comet assay, DNA damage was not observed in JSH-Ⅵ-3 and JSH-Ⅶ-3, wherase concentration of 32.8 $\mu\textrm{g}$/ml in JSH-II-3 and 13.9 $\mu\textrm{g}$/ml in JSH-Ⅶ-3 were induced DNA damage in the absence of S-9 metabolic activation system. Therefore, we suggest that JSH-Ⅵ-3 and JSH-Ⅶ-3 have no genotoxic effects but JSH-II-3 and JSH-Ⅷ-3 induce some mutagenicity and DNA strand breaks in mouse lymphoma cell line used this study.