Induced Mutation with Standard Mutagens 



The standard mutagens, EMS and BrdU, were evaluated for mutagenic 

 activity at several doses. Data pertinent to the mutagenicity of these 

 compounds are presented in terms of the parameters of equation [2] in Table 

 7-2. The estimated number of mutants per 10 viable cells (7) is plotted in 

 Figure 7-6 as a function of relative dose. By expressing the mutagenesis data in 

 terms of mutant cell frequencies per 10 viable cells, meaningful comparisons 

 between different compounds or different doses of the same compound could 

 be made. Applying the data to equation [3] , EMS was mutagenic at all doses 

 tested (q< 0.05). BrdU was mutagenic at five of seven doses tested, and 

 produced a complex dose-response pattern similar to those observed with 

 hycanthone methanesulfonate, and other compounds in different assays (12, 

 13). 



Induced Mutation with Other Compounds 



Forward mutation experiments employing doses of toxicant generally 

 yielding 20 percent survival or greater were carried out in replica with several 

 inorganic compounds, and an aqueous extract of JP-5 jet fuel. The data are 

 presented in Table 7-3 in terms of the parameters of equation [2] . These 

 compounds or mixtures were selected for evaluation as mutagens because they 

 were either known to have, or were suspected of having, carcinogenic 

 properties. Their mutagenic response in the CHO Cell/BrdU-VL system can be 

 divided into three classes: (1) Experiments with the oxides of arsenic and 

 selenium, lead acetate, and the chloride salts of cobalt and nickel, failed to 

 produce any auxotrophs; (2) tests with beryllium and chromium usually 

 produced auxotrophs, but never in sufficient numbers to support a conclusion 

 of induced mutation; (3) Experiments with cadmium chloride, manganese 

 chloride, and an aqueous extract of JP-5 jet fuel, also produce auxotrophs, 

 sometimes in sufficient numbers to suggest induced mutation by these 

 compounds. As indicated in Table 7-3, it was possible to obtain relatively large 

 numbers of auxotrophs with CdCl-,. Usually, however, observed mutant 

 frequencies were low. Cadmium chloride was found to be significantly 

 mutagenic in about 20 percent of experiments, as was the extract of JP-5 jet 

 fuel. Manganous chloride was observed to be mutagenic in approximately 50 

 percent of experiments. 



Isolation of Nonauxotrophic Variants 



Two classes of variants, other than auxotrophs, were isolated from cell 

 populations treated with known genetic toxicants. One class consists of cells 

 exliibiting a rounded morphology, and represents cells unable to stretch out on 



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