Epigenetics

Epigenetics is the topic that is now engulfing the genetic community.  What is epigenetics?  Well, literally it means “above genetics”.  But the actual meaning is much more complicated than that.  Epigenetics is not necessarily your DNA, or even genes for that matter.  But it does however determine how much or whether certain genes are expressed.  In other words, what happens to you genes over the course of your life.  The really interesting thing is, what your grandparents did 50 years ago, can actually affect you today via your genes.  That’s right, habits your parents or grandparents had can actually be expressed in you.  And the same goes for your children, and grand children.  The core of epigenetics is the binding of methyl groups to the DNA.  This tells cells to express certain parts of your DNA in certain areas.  Histones, or the protein DNA is wrapped around also have an expression effect.  How the DNA strand is wound around these histones can effect gene expression.   The tighter a histone is wound, the less of that gene is expressed.  And the looser a gene is wound, the more that gene is expressed.  An analogy I like to use is methyl groups are like a switch, and histones are like a knob for genetic traits.  If your genome was a computer, DNA would be the hardware, and epigenetics would be more similar to the software.  Your DNA will never change; it is the same your whole life.  However, epigenetictags can be altered through out your life. 

That being said, epigenetic information is not permanent.  The “epigenome” changes most during periods of change in our bodies.  For example, puberty or pregnancy.  But it changes suddenly at all stages of our life.   What we put into our bodies and what we do can be huge factors on these epigenetic tags.  Only in the last 20 years have we really started to understand these epigenetic tags.  In the past we thought these epigenetic tags were stripped from DNA before reproduction.  However, while some are, we are learning that many are not.  This is where we come to talking about how your daily routine, can effect your unborn children.  This is thought to be some of the reason that traits like alcoholism and drug use are often genetic.  Or at least have genetically rated probability.  We first came across this trend when a public health specialist took a look at dietary trends from generation to generation in Sweden.  They found that those who grew up in an era of plentiful food died 6 years earlier than those who grew up in periods of scarcity.  Here is the scary part; their kids death patterns followed a similar trend.  And this is where the first thought of epigenetics occurred.  There is however a bright side in this.  We used to always think genes were the end all be all, meaning we could not escape how they unfolded.  However this is not true. Living a healthy life style can improve your genes and possibly even silence bad ones.  So just because you have a certain gene for something, does not necessarily mean it is expressed. 

Biotransformation

Biotransformation is recognized as any altercation of a chemical within the body.   More specifically, biotransformation is the sum of all chemical processes of the body that modify endogenous or exogenous chemicals.  How biotransformation takes place, and the speed at which it does can be influenced by a lot of different factors.  In people these factors include things like age, sex, existing conditions, genetic variability, enzyme induction, and nutritional status.  Some people lack enzymes to break down certain chemicals.  For example, some people have a condition were they lack the enzyme to break down alcohol.  Humans are at there peak capability of processing chemicals that enter the body during early adulthood.  Then, as we get older, we start losing our ability to process these chemicals at the speed we used to.  Children cannot process chemicals as fast as adults due to a smaller body mass and not having developed certain concentrations of enzymes yet.   Differences in hormones from male to female can also play a pretty large role in determining how a body reacts to a chemical.  Nutrition also plays a large role, for several reasons.   Specific vitamin, mineral, and protein deficiencies can lead to lack of ability to produce enzymes at peak levels.  Some specific components that play a large role in creating these enzymes include, amino acids, carbohydrates, cofactors, and more.  Large portions of the reactions that are part of the biotransformation process happen in the liver exclusively.  Because of this, diseases that degrade the health of the liver like Hepatitis, reduce the rate of biotransformation in humans.  This can subsequently lead to even further health problems for the individual.  There is a whole science devoted to studying the effects of biotransformation.  Usually we will use animal models to predict the effects chemicals will have on humans.  This is a good method, but genetic differences between humans and animals may cause some difference in effect.  Now lets talk a little bit about how enzymes work.  Enzymes are biological catalysts.  They are high molecular weight proteins that allow for biotransformation to take place.  Enzyme deficiencies are somewhat common in humans, and can be very harmful to health.  Especially if there is an enzyme deficiency with no alternative way to break down that particular chemical.  As stated before many of these conditions are in fact genetic traits inherited from the parents of an individual.  This may require an individual to maintain a strict diet, often excluding certain foods, and eating healthy amounts of others.  Enzymes are often compared to a lock and key model when explaining how they interact with a substrate (chemical). 

A substrate may fit into an enzyme and trigger it, “turning the key”.  Or a substrate may fit enough into an enzyme to block it from bonding with anything else, but may not “turn the key”.  Enzymes may only absolutely catalyze one specific reaction.  However, chemicals that are similar structurally may have similar effects.   Or as stated before, fit into the enzyme but not trigger a reaction.  This is critical in toxicology, because two chemicals can be very similar, but one may be deadly and the other harmless.

Fluoride in Public Water

The addition of fluoride to our public water supply is a very controversial subject in today’s world.  It was observed that people who drank water containing a low concentration of fluoride had a lower rate of tooth decay.  And this is true; fluoride helps prevent bacteria from producing acids that decay tooth enamel.  But two much fluoride can also cause the pitting of teeth and other health problems.  In fact as low as 1.5ppm in water can cause tooth decay, and as low as 3-6ppm in water can cause skeletal decay and/or abnormalities.  And even in low concentrations, fluoride can build up in our bodies over time.  It is very quick to absorb into the body and enter the blood stream, than making its way through the rest of the body.  Some say it even can effect our pineal gland, and than brain function. 

However that is not necessarily a scientific fact.  It has also been claimed that the science from which our acceptable fluoride levels have been based off of, may be drawn from fraudulent or inaccurate studies.  It is difficult to separate proven facts from controversy in the topic of fluoride and its potential health effects.  You have a large number of people claiming side effects from fluoride that simply are not proven to be true.  On the flip side however, there are a lot of scary proven facts about fluoride exposure.   Today, around two-thirds of Americans have fluorinated water. In the 1940’s water treatment facilities’ started to add fluoride to the public water supply for dental health reasons as previously stated.  The fluoride that is being added to our water now is sodium fluoride, and it is actually a waste product of aluminum manufacturing.  This particular compound is more likely to cause fluorosis, which is the staining of the teeth with an opaque hue.  There is a lot of speculation as to using this compound, which is a waste product of manufacturing, and putting it into our bodies.  But it is in such low concentration; some say it is not an issue.  That being said, 97% of Western Europe still does not have fluoride in their water.  Many countries did have fluoride added initially but took it out.  Here is the surprising thing; the World Health Organization claims no significant difference in tooth decay between countries with, and without fluoride.   That makes us ask ourselves, is the benefit really worth the risk?  Alarmingly, 40% of American teenagers show some negative signs of fluorination.  It is usually in the form of plaque like stains.  For infants and young children, fluoride provides only risks.  This is considering they are not going to have the teeth they have now later in life.  Another fact I found particularly shocking, fluoride supplements have never actually been approved by the FDA in the United States.  Negative symptoms of fluoride are particularly evident in low income areas.  This is thought to be due to lower nutrition levels on average, and on average, low income adults are less healthy than there peers.  This inhibits the body’s ability to combat side effects from fluorine. 

Dose-Response

Toxicology as a science is based of the relationship between the dose of substance absorbed by an organism, and the response it triggers.  Paracelsus said it best when he stated, “the dose makes the poison”. 

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In other words, everything can be toxic in a way, in a certain amounts.  Even something as harmless as water can be harmful, if you drink too much of it.   Likewise very toxic substance may have no effect in very low doses.  But the key thing to take away from this, is the amount of a toxin is what determines the effect.  For example, we breathe in some CO2 in the air with every breath, but if we where to breath 100 percent CO2, we would die.  A more relatable method may be alcohol consumption.   Most are familiar with this dose-effect relationship.  Too much alcohol can make us sick/impaired, and eventually lead to death.  We refer to the lowest dose needed to cause an adverse effect as the threshold dose.  This is when an effect can first be linked to a certain chemical.  This is not the same in every organism however.  A 200lb man who drinks 4 beers may not feel a huge effect from the alcohol.  However, if a 100lb man drinks that same amount, he may feel much more of an effect.  Individuals can however be hyperresponvive, meaning they are just very responsive to a chemical for any of a variety of reasons.  And in contrast, an individual can be hyporesponsive, meaning they are particularly resistant to a toxin for whatever reason.  With all toxins, different people and different organisms react to them differently.  Some organisms can actually consume substances that would strike death to different species.  A dose that kills 50 percent of the individuals it is administered to is a LD50.  Meaning if you have 100 organisms, all given the same does, about 50 will die.  We also use a term called an ED50 or the effective dose (50).  Meaning this is the does were ½ the individuals will experience an effect from a chemical.  An administered or applied dose is the amount of a chemical presented to an absorption barrier.  Which is different than how much your body actually absorbs.  The absorbed dose is the term used to refer to the amount your body would actually absorb.  The delivered dose is similar; it is the amount of the chemical that is readily available to react with any cell or organ within the body.  Much of this information we get from lab animals.  Meaning we test these dose-response relationships in labs on rats, mice, etc.  However humans and mice are not the same organism, so not all data can be drawn in parallel to humans.  Other data we know on human dose response based on the actual past death/response of humans.  But toxicity does not deal with just chemicals necessarily.  For example, radiation can be toxic to humans and other organisms.  And we have LD50’s etc. for radiation just as we do for other chemicals.  Anything that is harmful to us can really be under the umbrella term “toxic” .

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American Association of Poison Control Centers

The American Association ofPoison Control Centers exists in order to prevent and treat poison disorders.  They association supports 55 poison treatment centers in the United States. The AAPCC says its goal is to actively advance the health care role and public health mission of its members through information, advocacy, education, and research.  The AAPCC puts an annual report out every year, documenting the instances of poisoning in the United States.  This part of the report is called the “NPDS” or National Poison Data System.  You can call the poison control number any time of day, 7 days a week.  The number will automatically direct you to the closest poison control center.  Regional Poison Control Centers must be staffed by a medical doctor and a qualified poison information specialist.  In 2014 alone, there was 2,165,142 human exposure calls.  Which comes out to about 6.7 people per every thousand in the general American population.

  (image: https://aapcc.s3.amazonaws.com/pdfs/annual_reports/2014_AAPCC_NPDS_Annual_Report.pdf )However, the AAPCC does not just service human poison exposures. They also service a variety of animal exposures, although in relatively small amounts compared to the amount of humans they service. Dog exposures being the highest-ranking animal exposure.  But not every call received by the AAPCC is an exposure.  Many of them are simply questions.   These questions may concern prevention, safety, or education.  Poison information is the most common call.   This year three-year-old children were the most likely to be poisoned in the United States, followed by 2 and 1 year olds. 

(image: http://www.poison.org/poison-statistics-national)Before the age of 20, males are more likely to be poisoned than females.  But after the age of 20, the roles switch and women become more likely to be exposed to poison.  Making the population most likely to be poisoned, children under six, in particular male children.  The most common substances for poison exposure in the U.S. are cosmetics and self care products.  This is than followed by cleaning substances, and analgesics.  The most common serious poisoning is analgesics, followed by fumes/gases/vapors.   In 2014, 85 percent of the exposures reported were non-toxic, minimally toxic, or at most had a minimal effect.  8 percent of these reported exposures were serious or even fatal.  Intentional poisoning are generally much more dangerous than unintentional.  There were 32 times more serious poisonings/deaths compared to unintentional poisonings.  As you can tell, the poison control center is very busy and services a massive amount of people.  In 2014, a poison exposure was reported once every 15 seconds.  92 percent of all poison exposures were reported in the home.  You can also excess a wealth of information on the AAPCC’s website.  You can find out how to use poison safety and store poison safely.  In 83.7% of exposures, ingestion is the route of exposure.   This is than followed by inhalation, and unknown routes.  Overall, the information on the AAPCC site and annual report is very useful.   It offers valuable information of trends in the United States.  This information is especially valuable in preventing future poisonings.  The AAPCC is supposed to be releasing another yearly report soon for 2015, giving us further incite into the trends of modern day exposure.