A supranutritional intake of selenium (Se) may be required for cancer prevention, but an excessively high dose could be toxic. Therefore, the effect on genome stability of seleno-L-methionine (Se-met), the most important dietary form of Se, was measured to determine its bioefficacy and safety limit. Peripheral blood lymphocytes were isolated from six volunteers and cultured with medium supplemented with Se-met in a series of Se concentrations (3, 31, 125, 430, 1880 and 3850 microg Se/litre) while keeping the total methionine (i.e. Se-met + L-methionine) concentration constant at 50 microM. Baseline genome stability of lymphocytes and the extent of DNA damage induced by 1.5-Gy gamma-ray were investigated using the cytokinesis-block micronucleus cytome assay after 9 days of culture in 96-microwell plates. High Se concentrations (>or=1880 microg Se/litre) caused strong inhibition of cell division and increased cell death (P < 0.0001). Baseline frequency of nucleoplasmic bridges and nuclear buds, however, declined significantly (P trend < 0.05) as Se concentration increased from 3 to 430 microg Se/litre. Se concentration (<or=430 microg Se/litre) had no significant effect on baseline frequency of micronuclei and had no protective effect against genome damage induced by exposure to 1.5-Gy gamma-ray irradiation. In conclusion, Se, as Se-met, may improve genome stability at concentrations up to 430 microg Se/litre, but higher doses may be cytotoxic. Therefore, a cautious approach to supplementation with Se-met is required to ensure that optimal genome health is achieved without cytotoxic effects.