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Mutagenesis Advance Access published online on January 20, 2009
Mutagenesis, doi:10.1093/mutage/gen074
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© The Author 2009. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

The effect of selenium, as selenomethionine, on genome stability and cytotoxicity in human lymphocytes measured using the cytokinesis-block micronucleus cytome assay

Jing Wu1,2, Graham H. Lyons1, Robin D. Graham1 and Michael F. Fenech1,*

1Nutrigenomics Laboratory, CSIRO Human Nutrition, PO Box 10041, Gouger Street, Adelaide BC, SA 5000, Australia 2Discipline of Plant and Food Science, School of Agriculture, Food and Wine, University of Adelaide, Australia

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 µg Se/litre) while keeping the total methionine (i.e. Se-met + L-methionine) concentration constant at 50 µM. 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 (≥1880 µg 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 µg Se/litre. Se concentration (≤430 µg 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 µg 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.

* To whom correspondence should be addressed. Tel: +61 8 8303 8880; Fax: +61 8 8303 8899; Email: michael.fenech{at}csiro.au

Received on October 21, 2008; revised on November 26, 2008; accepted on December 10, 2008.


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