Teratogens

Mutagenic agents are not the only source of birth defects and spontaneous abortions. Some substances are more properly classified as ter-atogens instead of mutagens. Teratogens are substances that cause malformation of the developing embryo but do not act through changes in the DNA. A helpful analogy to understand the difference between teratogens and mutagens is to consider a building and its blueprint. A mutagen changes the DNA blueprint for an organism. The building or organism is flawed because the originally correct blueprint is altered. A teratogen does not alter the blueprint, but rather causes a defect in the building by providing faulty materials or making mistakes in the building process. Both teratogens and mutagens may cause spontaneous abortion, severe malformation of the embryo, or mental retardation of the baby, but the underlying mechanisms are very different.

Why do substances, some of which do not cause any problems in an adult nor cause changes in the DNA, cause major defects in a developing embryo? Early developmental processes have an immense effect on the individual, both mentally and physically. Remember that each of us begins as a fertilized egg that must divide many times in order to make all the different cells of our body. In order to develop properly, cells must interact with neighboring cells, and some must even move over other cells to be accurately positioned. These cellular activities are very prominent early in embryonic development. Any untoward influence on cells during these critical early stages will affect the processes in progress and a great percentage of cells in the developing embryo.

An example of a tragic teratogen is thalidomide, a medication formerly prescribed for nausea. This medication is perfectly safe for adults, and so it was prescribed for morning sickness to pregnant women in late 1950s and early 1960s. It was only after a spurt of babies were born with deformed limbs that anyone realized that thalidomide is a strong teratogen. It turns out that the teratogenic effect occurs in the very earliest days of pregnancy, when limbs are just developing and when the mother may not even be aware that she is pregnant. It is now thought that thalidomide affects the formation of blood vessels, a critical process in early development. Because of this effect, thalidomide is now being considered for cancer treatment, since tumors also need a good blood supply to grow.

Box 8.1 Why There Were Few Thalidomide-Caused Birth Defects in the United States

We now know the tragic consequences of taking the drug thalidomide for pregnant women. However, when this drug was first submitted for use in the United States as sedative to the U.S. Food and Drug Administration (FDA) in the early 1960s, little information was available to suggest its potential dangers. The story of how a tragedy was barely averted in this country speaks well of drug-safety laws in the United States and exemplifies the efforts of one woman who fought pressures to allow thalidomide to be sold in the country.

Thalidomide was first made in Germany in 1953, and by the late 1950s it was widely used as a sleeping pill by adults and children. It also prevented common morning sickness due to pregnancy and was widely used for that purpose. In 1960, Merrel Company applied to the FDA to market thalidomide in the United States. By this time, laws in the States required that drugs be demonstrated to be both safe and effective. Years of thalidomide use in Europe had not detected any toxic effects of the drug. Thus many felt that it would

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