Somatotoxic is the condition in which one observes death of cells. This is not inheritable. If too many cells die as is found in cancer or an injury, the patient dies. Carcinogenic represents a change in cells; either a mutational change or perhaps a persistent irritant where the cells alter in their ability to survive; this is often the basis for cancer. Teratogenic refers to the causation of fetal abnormalities. As we study the genetics of reproduction two new words are introduced. Teratogenetic would be a mutagenic effect that may effect the embryo or the gonads (testes or ovary) of the embryo that would produce subsequent abnormalities in the second or third generation. This would then connote a reproductive detriment or difficulty in the ability of their children to have normal children and this may in fact not show up for 20, 40, or perhaps even 60 years. To put this in perspective, the flow sheet in figure 2 starts with the genetic molecule DNA and shows that if a genetic change occurs, the clinical effect can vary. If genetic change persists through cell division the ability of the cells to repair, or adapt to the mutation is reflected. This, of course, constitutes very little danger to the human race. If persistent abnormalities are found in skin or blood cells we can expect either malignancy or premature aging, both of which have been strongly inferred in LSD-like compounds. If chromosome damage occurs during embryonic development, there will be anatomic documentation of abnormal development. Our major area of concern is in the area which is yet unstudied, that is the danger to the developing sex cells, the sperm and the egg. Here we find that the potential genetic damage is great and one usually anticipates reduced fertility in the patient. In other words, the genetic damage is so great that persons exposed to certain mutagens are not able to have viable offspring. We hypothesize that many of these gametes may form developing fetuses that abort or result in abnormal babies. This effect again would show itself clinically in subsequent generations either by persistent sterility, repeated abortion, or abnormalities. Again to bring this into a more realistic area, figure 3 shows the three areas of a patient's life that concern us. In the adult patient, this would be the drug user whether pregnant or not, the time of exposure is critical to the developing fetus in estimating what the genetic risk would be. We compare equivalent radiation dosages and the probable significance comes in at the five roentgen level is one considers a lifetime dose. (In mutagens the exposure of 10 is more acute.) There is a gradual progression of all types of degenerative effects in the three age limits as has been well shown in various agents such as ionizing radiation, caffeine, alkylating agents, and other chemicals. Most of the cancer-treating drugs and in fact almost all of the cancercausing drugs can show exactly the same type of clinical progression. At the present time LSD shows a definite embryopathic effect. In addition, there is strong, inferential evidence there will be a reproductive detriment. However, we need to wait 10 or 20 years before one expects to observe the premature aging and the problem of increased incidence of cancer. Figure 4A shows the various types of chromosomal breakage. The term chromosomal aberration is used to define both breakage and structural abnormalities. Wherever there is an arrow you can see a break in the continuity of the black structure which would be the chromatid. In figure 4B is a ring chromosome; parts of its structure are broken and are usually translocated to other chromosomes. Occasionally you get second generation exchanges. All of these are grossly abnormal and recognizable in a double blind sample. Of course, all of our studies are analyzed in a blind system in which the slides are coded and we have no idea which patient they come from. We can usually tell from the culture slides what the extent of mutgenic exposure has been. In fact, one can usually estimate to what type of a genetically damaging agent the patient was exposed. Figure 5 shows mutagenic factors that have been studied. Good documentation exists on ionizing radiation, certain types of viral infections, certainly German measles which also causes chromosomal breaks, some chemicals in our environment, certain insecticides, selected drugs, environmental contaminants, and parental age. We emphasize the study of reproductive potential. As you know, the older an individual is, the greater the chance that they will have a defective offspring. In addition, death from cancer is correlated to advancing age. In addition to the naturally occurring mutagens (irradiation, virus, etc.) one observes multiple agents that fall withing the direct study of this committee (drugs, high energy sources, contaminants, etc.). Different test systems are available to observe chromosomes in the body. Peripheral blood culture is perhaps the easiest and best system to do serial studies. That is, by sampling peripheral blood one can study the induction of mitosis or cell division in the white blood cells. These white blood cells are similar to those found to be abnormal in leukemia. A drug (Colchicine) is used to stop the cells in culture and to prevent them from completing mitosis. The chromosomes are then swollen with a water solution and fixed. The cells are placed on a slide and |