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.
Safety Evaluation Laboratory, UBE Scientific Analysis Laboratory, Inc., 1978-6, Aza-okinoyama Oaza-kogushi, Ube-shi, Yamaguchi-pref. Japan.
Nobuyoshi
N
Fujii
Safety Evaluation Laboratory, UBE Scientific Analysis Laboratory, Inc., 1978-6, Aza-okinoyama Oaza-kogushi, Ube-shi, Yamaguchi-pref. Japan.
Shigemitsu
S
Yano
Safety Evaluation Laboratory, UBE Scientific Analysis Laboratory, Inc., 1978-6, Aza-okinoyama Oaza-kogushi, Ube-shi, Yamaguchi-pref. Japan.
Kenji
K
Takeshita
4-nitroquinoline 1-oxide; 8-oxoguanine; Ames test; Oxidative DNA damage; Reactive oxygen species