Cancer Initiation: Extending our 6th Generation Science model for Methyl Mercury Toxicology

Thursday, February 9, 2017

Extending our 6th Generation Science model for Methyl Mercury Toxicology

Introduction


 In previous posts, we discussed how biotechnology was changing the nature of medical science and somewhat arbitrarily assigned generations to each mode of scientific research, as they were introduced . We noted that in our model, a 6th generation study was one that took into account many, possibly interacting variables, that is, non-independent variables as inputs, and processed their impact on core systems related to genetic, epigenetic and immunological outputs. We went on to note that this type of thinking was already happening. In one relatively recent paper that we discussed, the authors uses single nucleotide polymorphisms ( SNPs ) related to single carbon metabolism as an input, and related their impact to four disease conditions that included cancer, Parkinsons and others.

The mathematics of non-independent variables


   While most of our traditional statistical models assume "independent" variables as inputs, in our models, we are using "non-independent" variables as inputs. In fact, we do not want to ignore or filter out interactions between variables, we want to find them. For example, what is the interaction between two SNPs, between a SNP and a toxin like methyl mercury, or an interaction between a SNP and a nutrient deficiency, for example in folate or b12.  As we discussed, the model that we use for this is called Dimension Reduction Analysis, were we wish to find interacting non-independent variables and combine them, producing a "dimension reduction" in our resulting model. A package for this is now supported and is available on the web.

Glutathione Detoxification of Mercury


  In our previous discussions, we discussed the Single Carbon Metabolism pathway and its evaluation using glutathione as a biomarker. We once again find that glutathione is an appropriate marker with respect to mercury toxicity. Here is a quote from our reference for the day, Andreoli (2017)[1]. What what we note is that our glutathione biomarker is a primary driver in the subjects attempt to detoxify mercury. Excuse, the length of this quote, but they are saying about what I would like to say.

      
Reduced glutathione (GSH-γ-glutamyl-cysteinyl-glycine), an essential tripeptide present in large quantities in all mammal cells, is the main agent of the glutathione detoxification system (GSHs). This system, which neutralizes the free radicals producing reactive oxygen species (ROS), protects cells against damage resulting from exposure to many external agents and oxidative stress. GSH, therefore, fosters a positive body’s response to the negative Hg actions towards natural detoxification process, and it is essential to heal the damage within the cells.
Various epidemiological studies have suggested that the response to Hg may be influenced by molecular variants in several regulatory GSHs genes, involved in absorption, distribution, metabolism and excretion process, better known as the Hg toxicokinetics, as reflected in Table 2. Consequently, the genetic component of human Hg susceptibility has now become another aspect not to be underestimated in this context
                                 Andreoli and Sprovieri ( 2017) [1]

At the risk of providing too much from our reference, I am going to add a brief comment from their discussion, which makes part of this articles point:
With the advances in genetics and high-quality information on Hg pollution, current research has shown that the interplay between genes and environment is critical to better understand the Hg impact on human health [87]. Despite the great potential, there has, however, been little use of genetic information in Hg risk assessments for both occupational and environmental exposures.
                               Andreoli and Sprovieri ( 2017) [1]

The Neglected Aspects 


   Andreoli goes on to discuss more pathways that are impacted by Methyl and inorganic mercury, but I would like to take a different direction. We know from our model is the Popeye Diet context that epigenetic processes ( that is DNA methylation ) is linked to glutathione and Single Carbon Metabolism. As such, ALL other pathways are potentially impacted by mercury, by the indirect impact of epigenetic mis-regulation. Time and time again, it is the Single carbon Metabolism pathway that is the most sensitive to toxic insult, and othery pathways follow suit,  presumably as a result of epigenetic mis-regulation.

Discussion 


  We know that auto-immune response is a result of mercury toxicity. Since this is my blog, I am going to go ahead and conclude that this is of failure to suppress Wingspans antigens, and their resulting stimulation of the immune system in those locations where cell division and active immune cells overlap ( the digestive system ) .

References


[1 ] Virginia Andreoli and Francesca Sprovieri Genetic Aspects of Susceptibility to Mercury Toxicity: An Overview Int J Environ Res Public Healthv.14(1); 2017 Jan [PubMed Central]


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