Preventive Effect of Preinduction of Metallothionein on Mutagenicity Caused by Benzo[a]pyrene

Abstract

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.