Genes and environmental toxisns
by C. A. Sharp
first published in Double Helix Network News, Fall, 2005, Rev. May 2013
Heightened public awareness of the effect of environmental toxins on human health has lead to greater concern about the effects these toxins may have on our dogs. There is no denying that things like PCBs, industrial waste and excessive soil concentrations of trace minerals pose health risks not only for humans, but for a wide spectrum of living things. Toxins not only cause illness by damaging body tissues, but may also have negative effects on our genes.
When it comes to illness, we tend to think of heredity and environment as two distinct issues. In actuality, genes always function within an environment. The genes in sperm, egg, and embryo are subject to the environment within the reproductive tracts of the individuals that produce them. Sperm will also be subject to the reproductive tract environment of the female into which it is secreted. Later, as portions of an embryo develop into different tissues, the environment in that tissue from genesis through the individual’s life will impact the genes within those cells. After birth and until death, things a dog ingests, breathes, or touches may bring substances into its body which might impact the function of genes.
In most cases these effects will be on genes in somatic cells. Almost all of the body is made up of somatic (non-reproductive) cells. Toxic exposure that causes gene mutations or chromosomal rearrangements can lead to cancer. In Scottish Terriers a clear connection has been demonstrated between exposure to lawn and garden herbicides and a certain type of bladder cancer. The reason this happens has yet to be determined but the herbicides apparently cause cancerous mutations leading to transitional cell carcinoma to occur in bladder tissue. The same study (Lawrence T. Glickman et al, April 2004) considered the possible effects of lawn and garden pesticides but found no correlation between those and the bladder cancer. Scotties are known to have a strong genetic predisposition to this cancer, but it is the interaction between those genetic factors and the environment, in this case often commonly used garden chemicals, that initiates the cancer.
Dogs are closer to the ground, likely to lie on it for extended periods and will sniff and lick things on or near the ground. They (usually) don’t wear clothes which might protect them from physical contact with environmental toxins. They will use their mouths to groom their coats and feet after having been outdoors. They are therefore much more likely than we to ingest substances like garden chemicals that post little or no threat to us because of our very different behavior.
Cancers can arise from exposure to toxins found indoors, as well. Dogs owned by smokers are far more likely to develop lung cancer, a very rare cancer in dogs, than are dogs owned by non-smokers.
Cancers are not the only type of disease that results from the interaction of toxins and genes. Immune mediated diseases are genetically predisposed. Some sort of environmental trigger is required to initiate the disease. The trigger does not change the gene; it causes the gene to act. If a trigger isn’t encountered, the dog remains healthy even though it carries the genes. Many things can provide a trigger, including infections, other diseases, or emotional stress. Toxic substances may play a role in some cases.
Drugs are, by their very nature, toxins. Dosage must be high enough to be useful for treatment but not so high as to cause serious side effects. Sometimes an otherwise safe medication can be toxic to some individuals because of their genetic makeup. The MDR1 mutation in Australian Shepherds and other collie-type breeds can cause extreme sensitivity to drugs that are used safely in other dogs. When the mutation is present, the dog will cannot clear certain drugs from the brain quickly enough. The drug level builds up to the point the dog may exhibit serious neurological signs and might even die.
Toxic effects on genes may occur not in the exposed individual, but in its offspring. Excess selenium in wetlands fed by irrigation run off in California’s Central Valley caused severe birth defects in wetlands birds. Birds are highly vulnerable to environmental toxins because of their high metabolism. Selenium is a trace mineral necessary in small amounts for good health, but in excess it is toxic. The selenium did not alter the genes of the baby birds; it interfered with their function during development. The clean-up of the affected wetlands has allowed healthy bird populations to rebound.
Exposing pregnant female mammals to certain toxins, particularly at key states of embryonic development, may lead to birth defects or even longer-range problems. Years ago a drug called Thalidomide was given to pregnant women in Europe suffering from morning sickness. Like the selenium in the wetlands birds, the drug, typically given early in pregnancy, sometimes resulted in severe limb abnormalities in the babies. In the mid-twentieth century women at risk for miscarriage were sometimes prescribed diethylstilbesterol (DES.) This drug not only affected the genes of the treated women, putting them at higher risk for developing breast cancer, their children may have developmental abnormalities or cancer. The daughters of women who took DES are at significantly increased risk of developing a particular reproductive cancer in young adulthood and may suffer a variety of reproductive failures. The sons of DES-users may have genital abnormalities and can be infertile.
Toxins may be harmful to your dogs and, in some cases, their offspring, but what does this problem mean for breeders? Can the effects of a toxin carry on for generations?
Most evidence indicates that they do not. The dog may get sick because of something it has eaten, inhaled or touched, but if the toxin is removed from its system before permanent damage is done, the dog should be fine and there should be no reproductive effect. As we have seen, some toxins will alter genes in the exposed individual or in offspring it is carrying at the time, but not on subsequent generations. If a toxin caused mutations in germ line (reproductive) cell DNA, there could be a multi-generational effect, but this is extremely rare if it happens at all.
However, recent research in the field of epigenetics has indicated that under some circumstances trans-generational effects might occur (Matthew D. Amway et al, June 2005.) Epigenetics is the study of heritable changes in gene function that occur without changes in the DNA itself. Researchers discovered that endocrine disruptors, toxins that interfere with reproductive hormones, given to pregnant mice will result in male offspring that have significantly lowered sperm counts and fertility. By itself, that is the sort of scenario we have already described with DES in humans and excess selenium in birds. But in this case, it didn’t stop with the sons of the exposed mothers. Those males’ sons, grandsons, and so on, also exhibited the same low sperm counts and fertility even though they had no exposure to the toxins themselves. No genetic mutations have been found in these mice. More recent research has demonstrated that these epigenetic effects can be seen even into the 4th generation, well beyond the point where the original environmental exposure could have directly altered the germ cells of descendants (germ cells of children are present in the womb and thus the grandchildren can be directly impacted by exposure.) As a result the effects of exposure to environmental toxins might in some cases be far more complicated than we imagined.
Toxins, natural and man-made, are part of our world and not something we can eliminate entirely. Some, like poisonous plants or venomous animals, can be readily avoided by not allowing them in our homes or yards and avoiding places they might naturally occur. We can minimize the risk of man-made hazards by cleaning them up or not allowing our dogs to be in contact with the substances. Drugs that may have toxic effects need to be monitored carefully. In the case of the MDR1 mutation, there is a genetic test, so dogs of susceptible breeds should have their genetic status determined before they receive any of the drugs for which they can be sensitive.
The buildup of toxic substances in our air, water and soil must be addressed through political and regulatory processes, as should the safe and proper use of beneficial chemicals with possible toxic effects. As individuals, the best we can do for our dogs and ourselves is follow directions when using chemicals or medications, clean up our immediate environment as best we can and, in Superfund-type worst case scenarios, move somewhere else.
Because of our general awareness of the threat toxins can pose and the truly horrific accounts we have all encountered in the news, we sometimes tend to assume anything that goes wrong with health is due to toxins. A hereditary disease, like primary epilepsy, for which there is no positive diagnostic test available, too often gets blamed on a real or unspecified toxic exposure because that is easier to live with than a serious inherited ailment that has implications for all the ill dog’s relatives. The truth is, for most of us and our dogs the risk of dangerous exposure to toxins is small. Jumping to the conclusion that a serious health problem must be due to toxin exposure without compelling evidence can lead to improper treatment for the ill dog, unnecessary feelings of guilt on the part of the owner, and, in the case of something that is hereditary, the production of more sick dogs when relatives are bred on the assumption that the disease was due to a toxin.
The good news is that severe toxic health effects are not nearly so common as sensationalist media would have us believe. In most cases the toxins do not alter DNA or gene function. Except in the case of a pregnant female, the toxin isn’t going to affect offspring. The bad news is, even though the risk isn’t high, it is out there and there is an indication that it might, in some cases, effect future generations. Keeping informed and remaining vigilant should keep most of our dogs safe from the genetic effects of environmental toxins.