Molecular dosimetry of chemical mutagens determination of molecular dose to the germ line

Abstract

To be able to extrapolate with confidence from the results of mutagenic tests with laboratory species to man, it is necessary to demonstrate our ability to extrapolate among laboratory test systems. In the three tier approach to mutagenic tests proposed by B.A. Bridges [ 5]; the first two tiers are essentially qualitative. That is, one asks only if a particular test system has a positive or negative response to the agents being tested; therefore, only the qualitative response of the test is extrapolated among laboratory test systems. Tier three, as proposed by Bridges, is far more demanding in that it asks for a quantitative estimation of the mutagenic risk-benefit type analysis in which the benefi t to mankind is weighed against the genetic risk of using the particular material in the environment. The most extensively studied mutagenic agent at the tier three level is that of ionizing radiation which is beneficial bo th for medical purposes and energy product ion and yet has been known to be mutagenic for many years. In the s tudy of ionizing radiation an ever increasing refinement of the quantitative estimation of risk is made and weighed against the potential benefit. This symposium will be concerned with meeting the dosimetry demand of chemical mutagens for this quantitative estimation of risk. In extrapolating from experimental organisms to man at the tier three level it is necessary to ask not only: Will the agent be mutagenic in but also: Can the mutational response in experimental species be related in a quantitative way to response in man?. Most experimental protocols confound the important question of gene t i c response with the physiological response; for example, will a material be metabolized in the same way in our experimental material as in man? In general, metabolism tends to vary among species more than does the genetic mechanism. In fact throughout the course of evolution the genetic mechanism has remained one of the most conserved elements of biology. Therefore, among diverse species, we would expect