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.
Sato
M
M
Division of Environmental Pollution Research, Fukushima Medical College, Japan.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis*; D009929:Organ Size / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism; D015032:Zinc / Q000378:metabolism
D013481:Superoxides; D003609:Dactinomycin; D008668:Metallothionein; D015032:Zinc; D010269:Paraquat