ABSTRACT
The genotoxicity of zinc was examined in 4 short-term mutagenicity assays. Zinc acetate produced dose-related positive responses in the L5178Y mouse lymphoma assay and an in vitro cytogenetic assay with Chinese hamster ovary cells, but was negative in the Salmonella mutation assay and did not induce unscheduled DNA synthesis in primary cultures of rat hepatocytes. Zinc-2,4-pentanedione produced frameshift mutations in Salmonella tester strains TA1538 and TA98, but did not induce unscheduled DNA synthesis in primary cultures of rat hepatocytes. The effect of ligand binding of zinc in the in vitro test systems is discussed.
Subject(s)
Zinc/toxicity , Animals , Chromosome Aberrations , DNA Repair/drug effects , In Vitro Techniques , Mice , Mutagenicity Tests , Mutation/drug effects , Salmonella typhimurium/drug effects , Time FactorsABSTRACT
Partially purified fractions of cytochrome P-450 were prepared from hepatic microsomes recovered from male rats 12 h after administration of either saline or polyriboinosinic:polyribocytidylic acid (poly I:C). Poly I:C reduced the microsomal concentration of cytochrome P-450 by 19% and decreased the maximal binding spectrum (delta Amax) resulting from addition of the type-II substrate 2,4-dichloro-6-phenylphenoxyethylamine to one fraction (B2) while increasing the affinity of that fraction for this substrate. Poly I:C also reduced the microsomal hydroxylation of benzo(a)pyrene and the N-demethylation of benzphetamine by the other fraction (B1). Since 14C-leucine incorporation into cytochrome P-450 was increased in poly I:C-treated rats, it is suggested that poly I:C depresses hepatic mixed-function oxidase activity by increasing the rate of degradation of specific cytochrome P-450s.
