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Figure 7-8. Mutation frequency induced by EMS and BrdU 

 as a function of expression time. 



human carcinogens; Neglect of the inorganics in this regard seems due, in part, 

 to the fact that such compounds comprise a relatively small percentage of 

 known or potential genetic toxicants, are difficult to handle in many 

 experimental situations, appear to mediate genetic effects by obscure 

 mechanisms, and have not been active in many major assays. Some metals have 

 shown activity in DNA repair tests employing microbial systems (37), and in 

 reverse mutation assays v^th E. coli (50). Recently, selenate and some 

 compounds of chromium have been shown to be active in selected strains of 

 Salmonella typhimurium (38). Perhaps the best assay developed to date for 

 predicting the potential genetic toxicity of metals is the in vitro 

 DNA-synthesizing system described by Sirover and Loeb, and which detects 

 copying errors in rephcating DNA (47). The fact that the carcinogenic metals 

 were not generally active in the CHO Cell/BrdU-VL system may reflect a 

 sensitivity problem related to the loss of mutants during selection to the effects 

 of starvation. Because mutation is periodically observed with certain of these 

 compounds, factors other than assay sensitivity may be involved. These factors 

 could be uniquely important to the expression of mutagenic activity by metals 

 and may not be presently under control or consideration. Extensive testing 

 with cadmium chloride and beryllium cliloride indicates that the problem does 

 not lie with expression time. 



95 



