Mutagenic effects of drugs

Although it is not known how much mutagenesis in man is due to drugs, concern that a serious problem may exist stems from a number of observations. Many substances have been shown to cause gene mutations in micro-organisms and in insects. The induction of mutations by some drugs has been demonstrated in mammalian systems and in human somatic cells. In man, significant frequencies of chromosome aberrations have been observed in spontaneous abortions and in newborn infants, although it is not known what part drugs might have played. The use of drugs that affect nucleic acids is increasing, both in children and in adults with non-malignant disorders, such as psoriasis, virus infections, and conditions associated with altered immunological reactivity.

Because of the genetic complexity of man, there are immense possibilities for mutation. There is no valid information regarding recent changes in human mutation rates because no systematic population monitoring has been performed. Genetic diseases are, however, becoming relatively more important owing to the reduction in the incidence and severity of parasitic and bacterial diseases. Two main types of genetic damage are recognized: chromosome aberrations and gene mutations. These may affect either somatic cells or germinal cells. Mutations occurring in somatic cells may lead to cancer or other degenerative diseases in exposed individuals, and a foetus may have congenital malformations. Although damage to either cell population may have serious consequences, from the public health stand point mutations in germinal cells are of paramount importance, as they present a hazard to future generations. Indeed, if mutations occur in a germ cell, they may be transmitted to the next generation and give rise to an individual all of whose somatic cells carry the mutant gene. This individual may then transmit the mutant to his offspring and later generations. Thus an increase in mutation rate will lead to an accumulation of harmful mutant genes in the population, and this in turn to increased incidence of hereditary diseases and a decrease in general health and well-being, with severe economic consequences to the society as a whole. While the relation between the ability of a chemical to produce mutations in experimental test systems and its ability to affect humans is not firmly established, the potential hazard to the population is of great magnitude.