MP7 Toxicogenomics in Environmental Studies
Monday, 14 November 2005: 8:00 AM - 5:30 PM in Exhibit Hall

(LUN-1117-791080) Functional toxicogenomic approach for assessment of risks and benfits associated with a methylmercury-contaminated diet.

Lundebye, A.-¹, Glover, C.¹, Sales, G.², Xheng, D.², Hogstrand, C.², ¹ NIFES, Bergen, Norway² Kings College, London, England

ABSTRACT- Methylmercury (MeHg) contamination of seafood can have a severe impact on human helath, with neurological effects during development of particular concern. However current MeHg risk assessments are potentially flawed in that epidemiological studies often do not consider positive health effects of seafood consumption or possible amelioration of toxicity by nutritional components, while laboratory experiments often do not account for the fact that most, if not all, MeHg in the diet is found as a cysteine conjugate, which is known to be less toxic than the widely utilised MeHgCl, at least in cell culture. As part of an ongoing research programme designed to address these concerns, we have conducted a study that attempted to establish the importance of MeHg speciation, and identify the mechanisms of MeHg toxicity in a murine model. Female mice were fed MeHg (as either MeHgCl or MeHgCys; 0, 2, 5, or 10 mg/kg diet) for a total of 8 weeks (3 weeks before mating, during gestation, and for two weeks following parturition). Assessments of neurobehavioural indices such as stress/anxiety response, reflex behaviour, locomotion and ultrasonic vocalisations were made in pups born to dosed dams. Brains of these pups were then subjected to microarray analysis to monitor changes in gene expression. These measures were accompanied by examination of Hg and MeHg tissue burdens. Preliminary results from these initial experiments will be presented. This approach offers advantages in that it elucidates sensitive biomarkers of toxicity, permits simultaneos exploration of numerous biochemical pathways that may contribute towards toxicity, while linking global molecular changes directly to biochemistry, physiology, behaviour and tissue burden. This functional genomic assessment of toxicity is likely to offer both excellent potential for deciphering complex biologiocal processes while providing key information for the development of improved environmental health policy.

Key words: methylmercury, toxicogenomics, risk assessment, neurotoxicity