Epigenetics and chemical damage in DNA which pass down generations in rats.

I have written before about epigenetics, the way that chemical compounds have an effect on our genes. We now know that chemicals can affect the way that our genes are switched on and off.

Recent work done in Washington State University on rats with compounds known as phthalates, which include compounds found in plastics and jet fuel, have shown that the changes they wreak can be inherited by offspring. Before we all go into panic mode about chemical damage to our DNA. The devil is in the detail, as is ever the case with any research involving epigenetics.

  • The dose of these chemicals given to pregnant rats were many hundreds of times higher than that found in nature.
  • The chemicals were given to rats at a time in pregnancy which involves rapid growth and change.
  • The changes in risk of disease in the rats offspring changes in the first offspring, and were different from the change in risk of the second generation; none of the first or second generation were exposed to the chemicals.

The first generation offspring had higher rates of kidney and prostate problems, whilst second generation had higher rates of disease of the testicles ovaries and more obesity. Females and males of the first generation when exposed to JP8 (a component of jet fuel) at a time when the gonads (ovaries and testes) were developing had more risk of prostate disease and kidney problems. The second generation who were not exposed to JP8 had more problems with polycystic ovaries and obesity. What does this mean in relation to DNA synthesis, repair and epigenetics in general? To be truthful not a lot at present as it asks more questions than it answers. These secondary questions however are very important.

  • Why does the effect of phthalates and JP8 differ from first to second generation after the primary chemical insult to the DNA?
  • What are the implications for humans?

We already know that taking certain drugs during pregnancy causes change in the  child – thalidomide being the most documented – but what of their children. In a scathing bit of comment in 1998 a paediatrician said that second generation birth defects was a media led fear.   Yet in another drug related mass tragedy reviewed in the Independent with Diethylstilboestrol (DES), the drug was given to women for 30 years up to 1973 for miscarriage risk reduction  It has since been found to cause a rare form of vaginal and cervical cancer in some of the daughters of the women who took it, as well as fertility problems. Beyond this there appear to be effects in the further generations of mothers born of women given DES.

Dr Julie Palmer, professor of epidemiology at Boston University’s school of public health, who is leading a study on the effects of DES exposure in second and third generations, said she does not think we have uncovered all the side effects of this drug. “Women who took it were given very big doses. They often took one pill every day, all the way through their pregnancy – sometimes a week before their due date,” she said.

 

Epigenetics: Most lifespan influencing genes affect the rat...

How does this chemical wreckage of the DNA occur, and why does there appear to be differences between the diseases that second and third generation children have higher risk for. Could it be that some epigenetic message received by the genome becomes hard-coded into the apparatus that supports and controls the DNA, thus becoming involved in inheritance? Could the change in disease type and risk between the generations be the result of the chromosomes and genes trying to undo the hard-coded defect caused by an epigenetic mechanism?

Epigenetics: DNA Repair Cycle

 

future post will look at DNA repair and how this occurs.

 

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