Studies on the mutagenicity of divalent metals has shown that in addition to cobalt chloride (Co2+), ferrous sulfate (Fe2+), cadmium chloride (Cd2+), and zinc chloride (Zn2+), manganous sulfate (Mn2+), and nickel sulfate (Ni2+), are mutagenic in Salmonella typhimurium. Mutagenicity was detected only when preincubation was done in distilled, deionized water or HEPES buffer. Phosphate buffer or components of Vogel-Bonner medium used in the standard mutagenicity studies, inhibited the mutagenicity of these metals. Studies of the specificity of mutagenesis in the different Salmonella strains have shown that metals can be detected as mutagens in both base-pair substitution and frameshift strains of Salmonella, and that the plasmid, pKM101, is required for mutagenesis. Chelators such as diethyldithiocarbamate (DEDTC) and 1,10-phenanthroline (PHEN) were used in attempts to overcome metal transport inhibition. DEDTC inhibited the mutagenicity of Co2+, Fe2+, Zn2+. Mn2+, but enhanced the mutagenicity of Cd2+. The mutagenicity of copper sulfate (Cu2+) was detected only in the presence of the chelator PHEN. Studies into the role of active metal transport are continuing, and preliminary results suggest that addition of glucose to the preincubation mixture, or an increase in the length of the preincubation exposure of cells to the metals, enhances the detection of some metals as mutagens. These data show that the traditional -inability to detect these metals as mutagens in Salmonella is not due to an inherent insensitivity of the Salmonella, but to the interaction of the metals with media components and/or passive and active transport processes.
