Cancer Initiation: November 2015

Monday, November 2, 2015

The foundatons of the emerging field of epigenetics provides the long sought link between development and cancer

In 1996 Pierre Beland released the book "Beluga - A farewell to whales" as a next step in the emerging field of environmental toxicology, or ecotoxicology.  The concept of transfer of biological toxins through the web of the food chain had already been introduced by Rachel Carsons "Silent Spring", but Beland added the next critical realization to our popular understanding by adding the observation that mammals, including us, have an extra level in our food chain which makes eco-toxins particularly harmful and insidious.
  It had previously been known that some agents which I am going to call eco-toxins, bio-accumulate as they rise through the food chain. Beland extends the bio-accumulation model to mammals, in this case, the whales of the St. Lawrence Seaway, and shows that these toxins achieve another level of bio-concentration in the milk of female mammals.  Thus, Beland's story is one of cancer, developmental failure and death, but the bio-chemical link between cancer development has remained somewhat of a mystery.
   Molecular biology and eco-toxicology was missing an important keyword - epigenetics.  As organisms and tissues develop, they accumulate methylation "marks" on the promoters of genes. Toxins that inhibit or interfere with the process methylating the CpG islands associated with promoters, likewise inhibit proper development and differentiation.
  Once an organism has reached an adult development stage, cells continue to divide in a "maintenance" stage. There are many genes in an adult somatic ( of the body ) cell that are suppressed in order to keep the cell out of the cell cycle. If the DNA methylation duplication system fails on an oncogene, or gene that causes a cell to enter the cell cycle, a cancer, or run away cell division can occur.
   In most cases, internal controls, or the immune system will catch these runaway cells.
 The immune system itself is dependent upon the mechanisims of differentiation. If the toxins has thus suppressed the immune system, then other cancerous cells can continue to divide and grow without natural inhibition.
  Thus, there is another chapter in the eco-toxicology model which is yet to be written. That is, using new molecular based tools to visualize and quantify how  individual "epigentic toxins" accumuate and lead to cancer and development failure.