Peripheral Blood Lymphocytes as Indicator Cells for in vivo Mutation in Man

Abstract

For the determination of the mutation rate of a single gene it is necessary to screen a very large number of the individual units chosen as testing objects. Single cell systems have been developed making possible the effective scoring of billions of cells in a short time. The mutants observed and counted are clones, originating from a single mutant cell. Most of the methods having microorganisms as testing objects use selective media in which only the mutants can grow out to colonies large enough to be scored by the naked eye. The same principles have been applied to mammalian cells, transformed to grow continuously, e.g., cell lines of Chinese hamster or humans. Results from such mutation tests are used for the risk evaluation of human exposure to genotoxic agents. However, the information gained in such tests about the genotoxic effects of a chemical in humans has limited value, mainly because human pharmacokinetic and metabolic factors are difficult to mimic. Therefore, there is great potential value in a mutation test performed with human cells constructed so that mutation can occur in vivo, the indicator cells can be withdrawn, and the mutant character can be developed in vitro.