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J.Health Sci., 56(1), 65-71, 2010
Preventive Effect of Preinduction of Metallothionein on Mutagenicity Caused by Benzo[a]pyrene
Masaki Takaishi,a Junko S. Suzuki,b
Masahiko Satoh,a, c and Hisamitsu Nagase*, a
aLaboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University, 5-6-1, Mitahora-higashi, Gifu 502-8585, Japan,
bResearch Center for Environmental Risk, National Institute for Environmental Studies, 16-2, Onogawa, Tsukuba, Ibaraki 305-8506, Japan and
cLaboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, 1-100, Kusumoto-cho, Chikusaku, Nagoya 464-8650, Japan
The effect of pretreatment with zinc (Zn) compounds on the mutagenicity of benzo[a]pyrene (B[a]P) was investigated using metallothionein (MT)-I/II null mice. MT-I/II null mice and wild-type mice were subcutaneously administered ZnSO4 once a day for 2 days and gavaged B[a]P at 24 hr after the last injection of ZnSO4. B[a]P-induced micronucleus frequencies were reduced by Zn pretreatment in the wild-type mice but not in the MT-I/II null mice. Zn administration significantly increased the concentration of MT in the liver and bone marrow cells of wild-type mice, but the statuses of other cellular antioxidants, such as glutathione, catalase and superoxide dismutase, were unchanged. In addition, the activity of a major B[a]P metabolic activation enzyme, cytochrome P450 1A, was unchanged by Zn treatment in both MT-I/II null mice and wild-type mice. These results suggest that Zn pretreatment protects against the mutagenicity of B[a]P through the induction of MT synthesis. The amount of MT produced in animals may determine their sensitivity to B[a]P exposure.
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