title: Effects of calcium(II) and magnesium(II) on nickel(II) uptake and stimulation of thymidine incorporation into DNA in the lungs of strain A mice.
abstract: The effect of calcium(II)acetate (CaAcet) and magnesium(II) acetate (MgAcet) on nickel(II) uptake in the lungs of strain A mice and on the nickel(II)-induced changes in the pulmonary DNA synthesis were studied in order to elucidate the mechanism(s) of inhibitory action of CaAcet and MgAcet upon nickel(II) tumorigenesis. Male strain A mice received a total of three i.p. injections, one every second day, of nickel(II)acetate (NiAcet), CaAcet, or MgAcet alone, or combined in a common solution. The single doses were 43 mumol NiAcet and 430 mumol CaAcet or MgAcet/kg body weight. To determine the uptake of nickel(II) by the lungs and pulmonary subcellular fractions, NiAcet labelled with 63Ni was used and the mice were sacrificed 2 days after the last injection. The [14C]thymidine uptake by the pulmonary DNA was determined at 6 h and 1-12 days after the last injection of metal salt(s). CaAcet increased nickel(II) uptake by the pulmonary cell mitochondria by 30%, microsomes by 40% and cytosol by 15%, compared with mice given NiAcet alone; nuclear nickel(II) levels were not affected. MgAcet decreased nickel(II) uptake in the nuclei by 15% and cytosol by 25%, and had no effect on the uptake by mitochondria and microsomes. A significant decrease of thymidine incorporation into pulmonary DNA was produced by NiAcet alone and CaAcet alone at 6 h to 2 days after the injection, followed by a single round of increased thymidine incorporation between days 3 and 6 after the injection. The mixture of NiAcet and CaAcet significantly increased the thymidine incorporation into pulmonary DNA without its prodromal decrease. MgAcet alone had no influence on the uptake of thymidine into DNA, except for a slight increase on day 5; but administered together with NiAcet it completely prevented the effects of nickel(II) upon thymidine incorporation. The results provide evidence that MgAcet, but not CaAcet, may inhibit tumorigenicity of NiAcet in the lungs of strain A mice by suppressing uptake of nickel(II) by the pulmonary cell nuclei and soluble fractions, and by preventing the effects of NiAcet on pulmonary DNA synthesis.
mesh_terms: D000085:Acetates / Q000378:metabolism* / Q000494:pharmacology*; D019342:Acetic Acid; D000818:Animals; D004261:DNA Replication / Q000187:drug effects*; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D013936:Thymidine / Q000378:metabolism*
chemical_list: D000085:Acetates; D008274:Magnesium; D019342:Acetic Acid; D013936:Thymidine