Genetic toxicology of metal compounds: An examination of appropriate cellular models†

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Abstract
Bacterial systems have not had success predicting metal carcinogenicity. Hypotheses explaining this failure are examined. Using a broad genetic endpoint, λ prophage induction, under sub‐toxic growing conditions, genotoxicity is seen for compounds of chromium, manganese, lead, molybdenum and tungsten. Copper, manganese, arsenic and molybdenum compounds enhanced UV mutagenesis in E. coli WP2. The toxicity of metal compounds to cultured mammalian cells correlates well with rat oral LD50 values. Whereas insolubility can present problems in bacterial studies, concentrations of metal compounds toxic to mammalian cells can be determined even in the presence of precipitate, and sometimes [Pb(NO3)2, BaCl2 and BeCl2] occurs only in its presence. PbS and MnS, which are insoluble, are much more toxic than the more soluble compounds Pb(NO3)2 and MnCl2. These results demonstrate the importance of cellular phagocytosis of insoluble metal compounds as a factor in studying the toxicity and genotoxicity of metal compounds.