In more than thirty years of intensive research and development in the field of bacterial mutagenicity testing, a wide range of strains with various, genetic endpoints has become available for routine studies. Selective genetic systems of great simplicity and handiness have been developed which assay for gene mutations, such as reversions from auxotrophy and forward mutations to antimetabolite resistance, lysogenic induction of prophages, and DNA repair. The introduction of techniques which take the mammalian metabolism into account, furthermore, makes bacterial systems potentially useful in (i) the primary identification of mutagens and non-mutagens and (ii) the quantification and ranking of relative mutagenic potency.
For primary identification purposes, sensitive strains of Salmonella typhimurium LT2 and of Escherichia coli B and K-12 with altered DNA repair capacities have been constructed which demonstrate a high predictive value for many chemical mutagens (and carcinogens). Comparitive studies showed that techniques using these strains can be efficiently standardized and calibrated. Several classes of chemicals with known mutagenic properties, however, are still not detected, or underestimated, in using standard assay procedures. Examples are presented of such compounds, which can be efficiently detected as mutagens upon -slight -modifications of the experimental conditions or the DNA repair capacity of the tester strains. It appears, therefore, advisable to modify and adjust the standard testing protocol to the particular type of chemical under study and to thoroughly calibrate the system with appropriate mutagenic and non-mutagenic reference compounds.
For the quantification of mutagenic potency, question remains whether bacterial systems will be of general usefulness. There are indications that the mutagenic activity of certain classes of chemicals, e.g., oxazaphosphorines, aflatoxins, nitroimidazoles, shows some proportionality with their chemical reactivity and that the relative degree of mutagenicity is similar in bacteria and in eukaryotic systems. The attractive possibility of employing in the quantification process those tester strains used for the primary identification 0340-5761/80/0046/0045/$ 03.20 appears, however, problematic, because (i) back mutation systems are rather specific in their response to certain mutagens and (ii) the use of strains with altered DNA repair and metabolism may lead to gross overestimations or underestimations of mutagenic potency in the corresponding wild types. More systematic studies are needed to determine the most representative genetic endpoints and genetic background under accurate determination of dose to the target molecule. The feasibility of such quantitative comparative studies has recently been demonstrated in a variety of organisms including bacteria, fungi, Drosophila, and mammalian cells in vitro and in vivo.
Proposals are made to use in further comparative studies chemicals, such as procarbazine, cyclophosphamide, and ethylnitrosourea, for which data on gene mutation induction in germinal cells of mammals are available.