Mutagenicity of cadmium in Salmonella typhimurium and its synergism with two nitrosamines.

Cadmium chloride (CdCl2) at concentrations of 0.5 mM was significantly mutagenic in Salmonella typhimurium tester strains and reverted histidine auxotrophy due either to missense (TA1975 and TA1535) or to frameshift (TA1537) mutations. It also induced forward mutations to 8-azaguanine resistance in each strain, but failed to increase mutation frequencies in strain TA100. More importantly, CdCl2 increased the mutagenicity of two common nitrosamines in synergistic fashion, at a level up to 30-fold greater than expected from simple additivity. The mutation frequency induced by N-methyl-N'-nitro-N-nitrosoguanidine was increased about 10-fold in the presence of 0.5 mM CdCl2. This synergism was seen both in the induction of 8-azaguanine resistance and the reversion of histidine auxotrophy and was observed in the repair-proficient strain TA1975 as well as its repair-defective (uvrB-) derived strain TA1535. The synergism was dependent upon Cd concentration and was much reduced at 0.25 mM CdCl2. The strongest synergism was observed in the reversion of histidine auxotrophy in TA1975 by 180 microM methylnitrosourea and 0.5 mM CdCl2. In contrast to mutagenicity, there was no evidence for synergism in the toxicity of CdCl2. These data suggest that cadmium might interfere with the repair of both spontaneous and nitrosamine-induced mutations. They also raise the possibility that cadmium and nitrosamines may have synergistic effects as environmental carcinogens.