Abstract
BackgroundWe 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).ResultsCu(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.ConclusionsOur 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.
Highlights
We investigated the enhancing effect of metal ions on several mutagens and examined their mechanism of action
To investigate the mechanism underlying the enhancing effect of metal ions on mutagenicity, we examined the production of reactive oxygen species (ROS), a known cause of oxidative stress, and 8-oxoguanine (8-oxoG), a DNA damage marker, in human lung carcinoma A549 cells [9,10,11]
The mutagens were dissolved in dimethyl sulfoxide (DMSO; Kanto Chemical Co., Inc., Tokyo, Japan)
Summary
Metal ions play crucial roles in biological systems within organisms. It is important to explore the synergistic effect of metal ions on mutagenicity and to evaluate the environmental and biological risks associated with them. Because the available data were obtained for a restricted number of mutagens and using different assessment methods, they are not comparable. It remains unclear whether metal ions have a selective effect on mutagenicity. This study, aims to investigate the effect of metal ions on mutagenicity. It is necessary that comparative data are obtained using sufficient kinds of metal compounds with the same counter ion and mutagens under identical experimental conditions. The Ames test (i.e., Salmonella mutagenic assay) is a biological assay used worldwide as a preliminary screening method to assess the mutagenic potential of
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