In addition, the level of Se deficiency routinely used in animal studies does not PI-103 compare Torin 1 directly with the marginal sub-optimal status observed in the volunteers on the study. Furthermore, animal models have different tissue distribution and expression of Se metabolising enzymes and, in particular, rats may not be ideal models to study effects of all forms of Se, in particular monomethylated species. In a longitudinal study of 39 human subjects, Sunde and colleagues found no correlation between mRNA levels of SEPW1, selenoprotein P, selenoprotein H, GPX1, GPX3, GPX4 and plasma Se over 24 weeks. The explanation proposed was that the volunteers were on the plateau of the response curve for these markers, and as such had a replete Se status with respect to expression of the molecular markers measured. However, the average plasma Se concentration was 1.1360.16 mmol/l whereas the average plasma Se in volunteers recruited on the present study was 1.2160.13 mmol/l. It is likely therefore that our volunteers were on the plateau of the response curve for SEPW1 and SEPR which would explain why supplementation with additional Se, up to 200 mg/day, did not produce a consistent significant change in gene expression of SEPW1 and SEPR. SEPW1 does, however, present an exception at week 10 where mRNA levels were negatively correlated with Se-yeast dose when a steady state Se status was achieved based on plasma Se data. This change in SEPW1 gene expression would not have been encountered by Sunde et al as their study focussed on differences in molecular markers over a range of habitual intakes estimated to be 27�C83 mg/day and the effect of Se supplementation on SEPW1 gene expression was not investigated. Supplementation with Se-enriched onions demonstrated a consistent, albeit relatively small, increase in the level of mRNA of all the selenoproteins tested, when compared with the unenriched onion group, particularly SEPW1. SEPW1 significantly increased in the Se-enriched onion group compared to the unenriched onion group. This result was as expected from in vitro work with Se-methylselenocysteine adapted human cells, as the predominant form of Se in onions is c-glutamyl methylselenocysteine. In contrast to the Se-enriched onions which contain,9% selenomethionine; the major form of Se in Seyeast is selenomethionine, constituting,60% of the Se content. Supplementation with 200 mg/day L-selenomethionine was shown to up-regulate expression of 28 genes but the individuals selected had arsenic-induced pre-malignant skin lesions and many of the genes found to be up-regulated were involved in immunological and oxidative stress regulation, which would likely have been differentially regulated in individuals suffering from this condition compared to healthy individuals.