ANALYSIS OF DOSE-RESPONSE PATTERNS IN MUTATION RESEARCH

Abstract

Mutation induction data in unicellular systems can be described mathematically within the framework of single-event Poisson statistics. This formal description can be linked to various mechanistic models for mutation and killing. Such mathematical links between formalism and mechanism enable use of the quantitative details of dose-response relations in drawing general inferences regarding the macromolecular processes involved in mutation and killing. Mutation yields, and in particular the position and magnitude of maximum yields, should be measured as carefully as possible as a means of verifying the apparent pattern of mutation induction kinetics suggested by double-logarithmic plots of mutation frequencies. For purely linear processes of mutation induction and exponential survival the maximum mutant yield is known to occur at the LD37 dose; however for non-linear kinetic patterns, the position and magnitude of the maximum yield shifts away from the LD37 in mathematically predictable ways. For any given pattern of killing and mutation, the ratio of the maximum mutant yields plotted over lethal hit units for 2 mutagens is a convenient measure of their relative mutagenic efficiencies.