Selective enhancing effect of metal ions on mutagenicity
Nobuyoshi Fujii1, Shigemitsu Yano1, Kenji Takeshita1
1Safety Evaluation Laboratory, UBE Scientific Analysis Laboratory, Inc., 1978-6, Aza-okinoyama Oaza-kogushi, Ube-shi, Yamaguchi-pref. Japan.
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.
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