250 
co 
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 with 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 replicating 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 chloride indicates that the problem does 
not lie with expression time. 
95 
