Mutation systems in cultured mammalian cells.

Experimental studies on the complex process of mutagenesis are conducted in the belief that they will increase our understanding of the effects of environmental agents on human populations. Cultured mammalian cells offer distinct advantages over other biological systems for studying this problem. Mutagenesis in cultured mammalian cells is unquestionably more relevant to man than are bacterial, fungal, or insect systems. At the same time, compared to whole-animal studies, cultured cells offer the advantage of ease of handling, low cost, and rapidity of assay. Mutation in cultured mammalian cells can be identified and measured at the phenotypic, protein, and DNA levels. Test systems have been developed to detect both gene and chromosome mutations. Direct evidence is available for true mutations occurring in mammalian cells, although some of the heritable variations could be epigenetic. It is now possible to identify the specific molecular alternations in mammalian cell mutants arising in vitro. The development of methods for the quantitation of mutation in cultured mammalian cells has been briefly considered in this presentation, particularly with reference to the choice of cell material, development of selective markers, and the various factors that affect quantitative measurement of mutations. Although notable progress has been made, much still remains to be learned to make these measurements more reliable. In applying the mammalian cell mutation assays for the screening of environmental mutagens, the choice of a system or systems should be based on their technical advantages and relevance to man. The basic parameters of the mutagen screening system must be well defined and controlled. The sensitivity for detection may be increased by the use of hypermutable cell strains. Appropriate statistical models to account for various sources of variability and the choice of statistical methods for the analysis of data are important considerations in screening environmental mutagens and carcinogens.