Selective enhancing effect of metal ions on mutagenicity

BACKGROUND: We investigated the enhancing effect of metal ions on several mutagens and examined their mechanism of action. We performed the Ames tests on six mutagens, i.e., 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, 4-nitroquinoline 1-oxide (4NQO), quercetin, 2-aminoanthracene (2-AA), benzo[a]pyrene, and 3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]indole, in the presence of five metal ions: Ca(II), Mg(II), Mn(II), Cu(II), and Zn(II). RESULTS: Cu(II) enhanced the mutagenicity of only 4NQO and reduced the mutagenicity of the other mutagens. Zn (II) enhanced the mutagenicity of only 2-AA. To clarify the mechanism underlying the enhancing effects of Cu(II), we examined the production of reactive oxygen species (ROS) and 8-oxoguanine (8-oxoG), a DNA damage marker, in human lung carcinoma A549 cells. Cu(II) induced a remarkable increase in intracellular ROS and 8-oxoG production in the presence of 4NQO. CONCLUSIONS: Our results suggest that the enhancing effect of Cu(II) and Zn(II) on the mutagenicity of specific mutagens is caused by an increase in ROS.