Metal-induced infidelity of DNA synthesis.

A number of metals have been demonstrated to be mutagens in procaryotic and eucaryotic organisms as well as carcinogens in experimental animals. Epidemiologic studies have indicated that Ni, Cr, and As are involved in human carcinogenesis. We have hypothesized that the active molecular species is the cation and that metal induced mutations result from incorrect base-substitutions during DNA replication. This is supported by the observations that metal ions diminish the fidelity of DNA synthesis in vitro using a variety of DNA polymerases. There is a significant correlation between the metals that decrease fidelity and those that have been reported to be mutagenic and carcinogenic. Thus, metal carcinogens are no exception to the general postulate that carcinogens can be identified by their effects on DNA.