Is the capacity of lead acetate and cadmium chloride to induce genotoxic damage due to direct DNA-metal interaction?

Even though the toxic effects of lead and cadmium compounds have been studi ed over many years, inconsistent results have been obtained about their mut agenic, clastogenic and carcinogenic properties. However, these metals are considered to be potential human carcinogens, The mechanism of metal-induce d carcinogenesis is still unknown, but one possible pathway may involve the interaction of metals with DNA, either directly or indirectly, In this wor k we explore the capacity of lead, cadmium or a mixture of both metals to i nteract with acellular DNA, by employing a variant of the comet assay. Our results, using low non-cytotoxic metal concentrations (0.01, 0.1 and 1.0 mu M) with the standard protocol for the acellular assay, showed an induction of DNA damage in cells of all organs studied; however, basal DNA damage was different in each organ. To confirm that we were working with pure DNA, pr oteinase K was added to the lysis solution. With this enriched-lysis soluti on we found a negative response in the induction of DNA damage in cells der ived from the liver, kidney and lung of CD-1 male mice. To support the resu lts obtained by the enriched-acellular assay, we studied the capacity of le ad and cadmium (0.1 muM) to induce breaks in pooled genomic DNA in cells of the same organs, with negative results. Consistent with these findings, th ese metals do not induce DNA breaks in the plasmid pUSE amp +. On the whole , we did not detect direct induction of DNA strand breaks by lead acetate, cadmium chloride or a mixture of both metals, all at low non-cytotoxic conc entrations. However, we found an induction of lipid peroxidation and an inc rease in free radical levels in the different organs of CD-1 male mice afte r inhalation of lead acetate (0.0068 mug/cc) Or cadmium chloride (0.08 mug/ cc) for 1 h, suggesting the induction of genotoxicity and carcinogenicity b y indirect interactions, such as oxidative stress.