Birth defects and the potential role of genetic differences in drug metabolism
Nebert, D.W.
Birth Defects Original Article Series 17(1): 51-70
1981
ISSN/ISBN: 0547-6844 PMID: 7284586 Document Number: 172629
A study of genetic differences in the metabolism of certain drugs can be made quite simple with the use of inbred mouse strains. Highly inducible levels of a drug-metabolizing enzyme (called cytochrome P1-450) reflect a mendelian dominant trait over low inducible levels, similar to brown eyes being a dominant trait over blue eyes. It is shown in these mice that the tendency to develop birth defects (and other intrauterine toxicity) depends upon the genetic predisposition of the individual embryo, rather than that of the maternal tissues. The experimental model system presented here provides an example that might explain clinically why sometimes only one child is affected with an apparent "drug-induced syndrome" although the mother has taken the same dose of the particular drug during each of 2 or more pregnancies. Of special interest in this study is the fact that the mother and the father both must be of a particular genotype before differences in birth defects among fetuses (due to their genotype) will be expressed.