Induction effect of coadministration of soybean isoflavones and sodium nitrite on DNA damage in mouse stomach

We have already found that nitrite-treated isoflavones exhibit genotoxic activities toward Salmonella typhimurium TA 100 and 98 strains (submitted: nitrite-treated genistein). However, we have not demonstrated genotoxic activity induced by simultaneous treatment with isoflavones and NaNO2in vivo. In the present study, we examined whether coadministration of isoflavones (such as daidzein and genistein) and NaNO2 induces DNA damage in the stomach of ICR male mice. Mice were coadministered with isoflavones (1 mg/kg body weight) and NaNO2 (10 mg/kg body weight), and dissected to collect tissues at 1, 3, and 6 h after administration. We used comet assay combined with repair enzyme formamidopyrimidine-N-glycosylase (FPG) to detect FPG-sensitive sites. An HPLC–ECD system was employed to determine 8-oxo-2′-deoxyguanosine (8-oxodG) in the stomach. In addition, we observed leukocyte infiltration by histopathological investigation, and measured total superoxide dismutase (SOD) in the stomach. We confirmed that oxidative DNA damage in the stomach was significantly increased by coadministration. Total SOD activities were also significantly stimulated by coadministration. However, the induction of inflammation in the stomach was not found. These data suggest that coadministration of isoflavones and NaNO2 can cause DNA damage in the stomach because of the formation of radicals.