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Dr. James Trosko (Michigan State University) was invited by Health Canada and the Canadian Institute of Health Research to speak at the CIHR Best Brain Exchange: Integrating Epigenetic Effects of Food and Environmental Contaminants into Risk Assessments Meeting on Tuesday March 19, 2013 in Ottawa, Ontario. A summary of Dr. Trosko’s presentation titled “Integrating Epigenetic Effects of Food and Environmental Contaminants into Risk Assessments” is included below.

Canadian Institutes of Health Research, Ottawa Ca, March 19, 2013:

“Integrating Epigenetic Effects of Food and Environmental Contaminants into Risk Assessments”

The Role of Nutritional/Dietary “Epigenetics” in Modulating the Risk to Acute & Chronic Human Diseases.

James E. Trosko, Ph.D., Center for Integrative Toxicology, Institute for International Health, Dept. Pediatrics/Human Development, College of Human Medicine, and Reza Nassiri, D.Sc., FACCP, Director of International Institute of Health, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan 48824, USA In the context of finite global resources for sustained healthy human survival, population explosion, increased environmental pollution, decreased clean air, water, food distribution, climate changes, changing gut microbiome, diminishing opportunities for human self-esteem, increased median life span, and interconnected causes of acute infectious and chronic diseases, the need to understand the factors leading to human diseases will be necessary for both the long term prevention and for managing short-term crises heath problems. There are but three mechanisms that can affect the pathogenesis of human diseases, such as birth defects, behavioral disorders, cardiovascular diseases, cancers, reproductive-and neuro-toxicological effects, and immune-reactions.

Those three mechanisms are: (a) mutations or “genotoxicity”, caused by either “errors in DNA repair or by “errors in DNA replication”; (b) cell death or cytotoxicity, caused by necrosis, apoptosis , etc. and (c) alteration in gene expression at the transcriptional ( DNA methylation; histone acetylation, etc,); translational levels ( m-RNA splice variants) or posttranslational levels ( mi-RNA effects and protein phosphorylation) or “Epigenetic toxicity”. Both natural agents (hormones, cytokines, growth factors; neurotransmitters, food components, products of food processing, biological toxins) and synthetic agents ( pesticides, food additives, pharmaceuticals, cosmetics) can trigger “epigenetic “ events. These epigenetic agents , by interacting with an organism, ultimately interact by extra-cellular communication with the three types of cells ( stem, transit amplifying cells and differentiated cells) , differentially, to trigger intracellular communication that either turn on or turn off genes, which, in turn, modulate gap junctional inter-cellular communication. These three integrated communication mechanisms exist in all organs of our body to regulate, homeostatically, the 5 choices a cell has when its internal physiology is altered by epigenetic agents. They can (a) proliferate; (b) differentiate; (c) apoptose; (d) senescence or (e) adaptively respond.[ 1]These are mutually exclusive choices a cell makes depending on the intracellular changes induced by the extracellular communicating molecule.(Figure 1)

Figure 1.

These epigenetic agents can be species-specific, gender specific, developmentally specific, organ –specific. They also work at threshold levels. They are effective in the absence of anti-epigenetic agents; they can work with other agents, additively, synergistically, or antagonistically. Depending on the biological context, they can have “good news-bad news” characteristics (retinoids, thalidomide, genistein, ATBC and CARET trials).

On a completely different level, the role of nutritional/food epigenetic effects must be viewed from an interaction of our biological and culturally evolutionary history. [2, 3] The transition of our pre-human geographical-determined biological evolutionary- nutritional requirements for survival to our current unequal and culturally- shaped diet has created a biologically mis-matched human nutritional experience. While genetic, gender, and developmental stage factors contribute to human diseases, various environmental and culturally-determined factors are now contributing to both acute and chronic diseases. The transition from the hunter-gatherer to an agricultural -dependent human being has brought about a global crisis in human health. Initially, early humans ate seasonally-dependent and calorically-restricted foods, during the day, in a “feast or famine” manner. Today, modern humans eat diets of caloric abundance, at all times of the day, with foods of all seasons and from all parts of the world, that have been processed and which have been contaminated by all kinds of factors, due to a diaspora of crops and global climate changes. No longer can one view, as distinct, infectious agent –related human acute diseases from chronic diseases. Given the predicted increase in the number of new births before the end of this century, a serious effort must be made to provide a healthy in utero environment for the most vulnerable stage of human development in order to prevent alterations in organ-specific adult stem cell numbers and stem cell –based diseases later in life. This new concept provides a mechanistic explanation for how pre-natal maternal environmental or dietary exposures can now affect diseases later in life (Barker Hypothesis). Studies of the atomic bomb survivors should illustrate this insight.

REFERENCES

1. Upham, B.L. and Trosko, J.E., “Carcinogenic tumor promotion, induced oxidative stress signaling, modulated gap junction function and altered gene expression”. Antioxidants & Redox Signaling 11: 297-308, 2009.
2. Trosko, J.E., “The gap junction as a ‘Biological Rosetta Stone’: Implications of evolution, stem cells to homeostatic regulation of health and disease in the Barker Hypothesis”. J. Cell Commun & Signaling, 5; 53-66, 2011.
3. Trosko, J.E. “Pre-natal Epigenetic influences on acute and chronic diseases later in life, such as cancer : Global health crises resulting from a collision of biological and cultural evolution.. J. Food Science & Nutrition 16: 394-407, 2011.