Commonly-Used Drugs Can Wreck Your Genes

by Bill Sardi

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Your genetic makeup may not be as fixed and unchanging as first believed.

Not yet a decade into the post-genomic era, following the discovery that humans have about 35,000 genes, researchers have discovered that there are inherited physical or mental traits that are not explained by sequences of DNA in the human genetic ladder or by environmental factors.

While inherited genetic information from your parents and grandparents remains relatively static, there are mechanisms whereby genes can be turned on (expressed) or turned off (silenced). This is the relatively new field of biology called epigenetics.

Your epigenome

All of the genetic information in humans is packaged in chromosomes in every cell in the human body. This body of genetic information is called the human genome. While the human genome is somewhat fixed, the epigenome is dynamic and responsive to environmental factors, chemicals (drugs) and the diet.

Furthermore, it has become increasingly apparent to biologists that chemicals can turn genes on or off even long after exposure. Epigenetic changes may not only linger, they may last a lifetime, particularly if they are induced during early development. [Human Molecular Genetics 2006 Oct 15; 15 Spec No 2: R131—7]

Biologists now claim "the epigenome is dynamic and responsive to environmental signals not only during development, but also throughout life; and it is becoming increasingly apparent that chemicals can cause changes in gene expression that persist long after exposure has ceased." [Medical Hypotheses June 4, 2009 online]

Mechanisms now understood

The two complicated mechanisms which trigger changes in the epigenome, alteration of DNA methylation (replacement of hydrogen atoms with methyl groups) and alteration of chromatin (the packaging of DNA strands around spools called histone bodies), are now understood. Chemicals, particularly drugs, affect both of these mechanisms that control the epigenome. [Indian Journal Medical Research 2006 Jan; 123(1):17—24]

Epigenetics and drug safety

In fact, the first application of epigenetics has been directed toward the evaluation and safety of drugs. [Toxicology Applied Pharmacology 2004 May 1; 196(3):422—30]

Do drugs favorably alter the human epigenome? The shocking early answer appears to be no.

Researchers now hypothesize that commonly-used, FDA-approved pharmaceutical drugs can cause persistent epigenetic changes. Researchers now propose that epigenetic side-effects of pharmaceuticals may be involved in the etiology of heart disease, cancer, nerve and mental disorders, obesity, diabetes, leukemia, bipolar disorder, schizophrenia, infertility, and sexual dysfunction. [Metabolism Clinical and Experimental 57: (2008) S16—S23] They are calling for epigenetic screening of all existing and future pharmaceutical drugs. [Medical Hypotheses June 4, 2009 online]

Researchers claim, if their hypothesis is correct, that the "consequences for modern medicine are profound, since it would imply that our current understanding of pharmacology is an oversimplification."

Up till now, epigenetic review of pharmaceutical compounds has been absent. Toxicologists have narrowly focused on whether drugs cause cancer in their safety screening of drug molecules. This may be why so many drugs are now being recalled after gaining FDA approval based upon small-group studies.

Persistent chronic exposure to some chemicals in drugs may eventually induce permanent changes in the human epigenome, producing latent, lasting or periodic effects, based upon exposure patterns (compliance to drug regimens).

Drugs that are known to cause epigenetic changes include statin cholesterol-lowering drugs, antidepressants, beta blockers used to treat high blood pressure and heart problems, anti-cancer drugs like tamoxifen and methotrexate, anti-inflammatory agents like Vioxx, even anesthetics, oral contraceptives and some classes of antibiotics. All of these drugs are fraught with chronic side effects. Some patients are exposed to more than one drug that may unfavorably alter the epigenome.

Permanent changes in the epigenome

Researchers are most concerned that drugs may produce defects in subsequent generations. They speculate that the current diabesity epidemic may be hastened by drugs. They say "it would be alarming if the worldwide increases in diabetes and obesity, which have been postulated to be epigenetic, were actually being accelerated by the increasing use of pharmaceutical agents." [Medical Hypotheses June 4, 2009 online] Most anti-diabetic drugs cause weight gain and eventual complete dependency upon insulin for blood sugar control.

Epigenetic Therapy

Epigenetic therapy is a new and rapidly developing area of medical exploration aimed at correcting epigenetic defects, particularly because these defects are thought to be more amenable to reversal compared with genetic defects.

Epigenetic therapeutic agents may prevent disease, opening up what biologists now call the "pre-symptomatic era" of modern medicine. [Human Molecular Genetics 2006 Oct 15; 15 Spec. No. 2: R131—7]

A primary target application is the pervasive diabesity epidemic in developed countries. For example, the common measure of blood sugar control, hemoglobin A1c, explains less than 25% of the variation in risk of developing diabetic complications. But a transient rise in blood sugar may produce a prolonged epigenetic effect that last up to 6 days even when normal blood sugar levels have been restored. [Journal Experimental Medicine 2008 Sep 29; 205(10):2409—17]

Epigenetics is now even poised to address the very reasons why humans age at varying rates. [Current Opinion Immunology 2009 June 3 online]

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