A combined Ames and in vivo genotoxicity assessment of dimyricetin-yl-diselenide, a structurally defined organoselenium flavonoid.

Dimyricetin-yl-diselenide (DMS; 3,5,7-trihydroxy-8-[[3,5,7-trihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl)chromen-8-yl]diselanyl]-2-(3,4,5-trihydroxyphenyl)chromen-4-one) is a structurally defined organoselenium flavonoid dimer in which two dihydromyricetin units are linked via a diselenide (Se-Se) bond. Due to the potential redox activity and thiol reactivity of certain selenium species, a systematic genotoxicity evaluation is required prior to further application. Therefore, in the present study, the genotoxic potential of DMS was assessed using a bacterial reverse mutation (Ames) assay and two in vivo assays in mice, namely the mammalian erythrocyte micronucleus test and the bone marrow chromosomal aberration test, in accordance with relevant Chinese and OECD Test Guidelines. The selected in vivo dose levels were based on acute oral toxicity data showing that the LD50 of DMS was greater than 5 g/kg BW in mice, thereby supporting the use of high-dose settings for genotoxicity assessment. In the Ames test, DMS (625-5000 μg/plate) did not increase revertant colony counts in five Salmonella typhimurium strains (TA97a, TA98, TA100, TA102, and TA1535), either in the presence or absence of S9 metabolic activation, while all positive controls showed expected responses. In the in vivo micronucleus assay, DMS (1.25-5.0 g/kg body weight, BW) did not affect the PCE/RBC ratio and did not increase the frequency of micronucleated polychromatic erythrocytes in either sex. In the bone marrow chromosomal aberration test, DMS (0.625-2.5 g/kg BW) did not increase the frequency of aberrant metaphase cells compared with the negative control, whereas cyclophosphamide induced marked increases in chromosomal aberrations. Collectively, DMS did not exhibit mutagenic, clastogenic, or aneugenic effects under the experimental conditions employed. These findings provide initial evidence supporting the safety profile of DMS and its potential for further development as a functional food ingredient or therapeutic candidate.