Ayotte et al. mercurials (Debord et al. 2003; Gonzalvo et al. 1997). Although the cysteine-285 resi- due does not seem essential for the enzyme activity (Sorenson et al. 1995), binding of MeHg to the thiol group could alter the active site of enzyme and in turn reduce its catalytic activity. This mechanism has been implicated in the inhibition of different enzymes by MeHg, such as thioredoxin (Carvalho et al. 2008) and arylamine N-acetyl transferase-1 (Ragunathan et al. 2010). Interestingly, we observed that blood selenium levels appeared to oppose the effect of blood mercury levels on plasma PON1 activity. Selenium is pres- ent in the active site of several enzymes, such as thioredoxin reductase, which is involved in redox regulation (Carvalho et al. 2008), and glutathione peroxidase, which protects from oxidative stress (Rayman 2009). Further studies are needed to identify selenium species that are present in selenium-rich food items consumed by the Inuit (e.g., beluga skin) and to decipher the mechanism through which selenium intake might protect against MeHg- induced toxicity in the Inuit population. A strong point of the present study is its sampling design that allows a proper repre- sentation of the Inuit population of Nunavik. Furthermore, to document the precision of the PON1 activity measurement, we included in each analytical batch a plasma sample that had been obtained from a volunteer at the beginning of the study, processed and stored frozen in the same conditions as the popu- lation samples. Finally, we determined the genotypes for three SNPs that are known to affect the expression of PON1 or its catalytic activity. This allowed us to verify whether interactions between mercury exposure and PON1 gene variants that had been noted dur- ing in vitro experiments could be observed in the Inuit population. There is no consensus regarding the optimal substrate to measure PON1 activ- ity in relation to cardiovascular diseases. Some authors measured the activity of the enzyme toward paraoxon (Ferré et al. 2003; Mackness et al. 2003), others used phenyl- acetate (Jayakumari and Thejaseebai 2009), and still others measured the activity toward two substrates, usually paraoxon and diazoxon (Costa et al. 2005). We used a commercial kit, the EnzChek Paraoxonase Assay Kit from Invitrogen, to measure the PON1 activity in plasma samples of our participants. Recently, Yang et al. (2010) reported that PON1 activ- ity, as measured by the same commercial kit, was associated with early structural and functional changes of arteries in a group of 156 hypertensive patients. Furthermore, in the present study, polymorphisms that were previously shown to influence PON1 catalytic activity or expression also modified PON1 activity, in the expected direction. We are 1082 looking forward to testing whether PON1 activity as measured by this commercial kit will constitute a useful biomarker to pre- dict the risk of cardiovascular disease in this population during the follow-up phase of the cohort study. Conclusion Results of this cross-sectional study suggest that MeHg exposure exerts an inhibitory effect on plasma PON1 activity. In addition to being a source of exposure to MeHg, marine foods that are part of the traditional Inuit diet are rich in selenium and n-3 PUFAs that may offset inhibitory effects of MeHg on PON1 activity. Dietary changes leading to a decrease in intake of these nutrients could lead to lower PON1 activity and, in turn, increased risk of CHD. Follow-up of the participants is indicated in order to monitor dietary changes and possible related modifications in biomarkers of cardio- vascular risk, including PON1 activity. Ref Rencs Aviram M. 2000. 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