Dose-dependent increases in metallothionein synthesis in the lung and liver of paraquat-treated rats.

Dose-dependent changes in the concentration of metallothionein-1 (MT-1) in rat tissues were determined following subcutaneous administration of paraquat (PQ), a superoxide radical-generating agent. At 24 hr after injection. MT-1 concentrations in the lung increased linearly with PQ dose. Concentrations in the liver increased with dose until a plateau was reached at a dose of 30 mg/kg body wt. In the kidneys, MT-1 concentrations did not increase even at high doses of PQ. Zn was the principal metal bound to MT in the liver. PQ-induced MT-1 synthesis may reflect de novo protein synthesis, since the increase in MT-1 in the liver was reduced by pretreatment of the rats with actinomycin D. Although MT-1 synthesis in the liver was well correlated with lipid peroxidation, as evaluated by measurement of thiobarbituric acid-reactive substances, there was no such correlation in the kidneys. PQ increased the lipid peroxidation in kidneys without any increase in MT-I content. The data suggest that enhanced lipid peroxidation is not necessarily related to the increased MT-1 synthesis caused by radical-generating agents.