Lessons From Radiation Genetics
Introduction
The last three decades have witnessed substantial progress in the development and use of a variety of in vitro and in vivo assay systems for the testing of environmental chemicals which may pose a mutagenic hazard to humans. This is also true of basic studies in chemical mutagenesis on mechanisms, DNA repair, molecular dosimetry, structure-activity relationships, etc. However, the field of quantitative evaluation of genetic risks of environmental chemicals to humans is still in its infancy. This commentary addresses the question of how our experience in estimating genetic risks of exposure to ionizing radiation can be helpful in similar endeavors with environmental chemical mutagens.
RADIATION GENETIC RISK ESTIMATION: BACKGROUND
Systematic efforts at quantifying the adverse genetic effects of exposure of human populations to ionizing radiation began in the mid-1950s and still continue. During these four decades, the conceptual basis, the methods used, and the risk estimates themselves have all been evolving. Up to the early 1980% this evolution was driven primarily by advances in mammalian radiation mutagenesis studies, with much less impact from advances in human genetics. The situation is changing and it is now clear that in the coming decades, progress in this area will be intimately linked to advances in the human genome project. There are at least two reasons for this: l ) genetic risks are expressed in units of inducible "genetic disease" and 2) advances in human genetics are providing important insights into the nature and mechanisms of origin of naturally occurring genetic diseases; therefore, they provide a basis for inferences on their inducibility by radiation.
Naturally Occurring Genetic Diseases
Consensus estimates of prevalence of naturally occurring genetic diseases in man are given in Table I. These diseases are traditionally classified into mendelian, chromosomal, and multifactorial ones. Mendelian dis-