Effects of flavonol derivatives on the micronuclei formation by N-methyl-N′-nitro-N-nitrosoguanidine and the enhancement of bleomycin-induced chromosome aberration by N-methyl-N′-nitro-N-nitrosoguanidine

Flavonol derivatives were tested for their anticlastogenic effect against induction of micronuclei by N-methyl-N′-nitro-N-nitrosoguanidine(MNNG), and against induction of chromosome aberration by bleomycin or MNNG/bleomycin. For micronucleus assay, each flavonol derivative (0, 0.001, 0.01, 0.1, 1, 10 and 100 mg/kg) was administered orally twice with 24 h interval, together with intraperitoneally administered MNNG (150 mg/kg). The results showed that most flavonol derivatives tested were effective in suppressing the frequencies of micronuclei induced by MNNG. For chromosome aberration assay, each flavonol derivative (0, 0.1, 1, 10, and 100 mg/kg) was administered to mice orallyin vivo, and then mice were sacrificed and spleen lymphocyte cultures were made. Bleomycin (3 μg/ml) was treated to the mouse spleen lymphocyte cultures at 24 h after con A initiation. There were no marked decrease tendencies in chromosome aberration unless all doses of galangin and some doses of several flavonol derivatives tested. In the another experiment, we have evaluated the effect of flavonol derivatives on the enhancement of bleomycin-induced chromosome aberration by MNNG. Most of flavonol derivatives reduced the incidence of chromosome aberration induced by in vitro treatment of bleomycin followed byin vivo treatment of MNNG. Galangin particulary showed a dose-dependent decrease tendency. Other flavonol derivatives showed slightly decrease tendencies although there were no dose-dependent relationships. These results suggest that most of flavonol derivatives may be capable of protecting the inibition of DNA-repair by MNNG. Our data indicate clearly that flavonol derivatives can suppress MNNG-induced genotoxicity such as an induction of MNPCEs. Therefore, our results could suggest that flavonol derivatives may be useful as a chemopreventive agent of MNNG.