Further Thoughts on Mercury, Epigenetics, Genetics and Amyotrophic Lateral Sclerosis

mercury body burden. They correctly point out that chelation-provoked urinary mercury levels may not reflect the amount of mercury to which motor neurons (or the brain) are exposed. However, it must also be considered that such ‘chelation challenge’ testing is subject to potential interactions from a variety of nutritional factors, such as blood thiol levels, zinc levels, selenium levels and other factors as discussed previously [3] . Each such factor represents a potential confounding variable that may go some way towards explaining the conflicting results found wherever chelation challenge tests are used in practice. An additional concern regarding chelation challenge testing revolves around the large bolus doses that are often used and may carry inherent risks, both from the side-effects of the chelators themselves and the potential to redistribute body burdens of mercury [3] . A further consideration is that while it is possible that mercury exerts toxicological effects through epigenetic mechanisms, we must not overlook recent discoveries of conventional genetic polymorphisms that have been associated with atypical neurobehavioural responses on exposure to mercury. Polymorphisms of CPOX, BDNF, 5-HTTLPR and COMT have all been associated with atypical neurobehavioural responses on exposure to mercury in combination with carriage of the relative gene I read with interest the recent paper by Callaghan et al. [1] reviewing the role of exposure to the metals lead, mercury and selenium and potential epigenetic factors in the development of amyotrophic lateral sclerosis (ALS). Callaghan et al. [1] have considered whether heavy metal interaction with epigenetic phenomena that govern DNA modifications such as DNA-bound histones, DNA methylation and chromatin remodeling may be responsible for some of the toxic actions of heavy metals which in turn may play a role in the etiology of ALS. Several aspects of their discussion regarding mercury in particular caught my attention. With regard to mercury interfering with epigenetic mechanisms, it has been observed previously that cysteineS -methylmercury conjugates are structurally similar to methionine, and are suspected to function as molecular mimics of methionine at certain amino acid transporters [2] . This being the case, and given that methionine plays a role in providing methyl groups to DNA methyltransferase, it is worth considering: might molecular mimicry of methionine allow organic mercury conjugates to interfere with DNA methylation thereby exerting epigenetic toxic effects? Moving away from epigenetic considerations, Callaghan et al. [1] discuss the use of chelators to estimate Received: October 4, 2010 Accepted after revision: January 21, 2011 Published online: March 16, 2011 D i s e a s e s