Role of metallothionein in the zinc metabolism of Ehrlich ascites tumor cells
The reactions of zinc and zinc, cadmium metallothioneins with apocarbonic anhydrase have been studied. Apo-carbonic anhydrase abstracts zinc from zinc metallothionein and zinc, cadmium metallothionein in second-order processes which are two to three orders of magnitude more rapid than those of EDTA abstraction of zinc and are similar to the rate of reconstitution of the apo-enzyme by unligated Zn. In comparison with other proteins, zinc metallothionein contains unusually reactive metal binding sites suggesting this protein may be a physiological donor of Zn to zinc requiring sites in cells. When limiting amounts of dietary zinc stimulate the deficient cells to divide, zinc is not observed in metallothionein. A non-limiting amount of dietary zinc supports both proliferation and the steady state presence of zinc in this protein. Zinc metallothionein is shown to be the principal donor of zinc to added apo-carbonic anhydrase in Ehrlich cell cytosol. Treatment of cells with a copper ligand known to possess anti-tumor activity, with the toxic metal Cd, or with cis-dichlorodiamine Pt(II) which is another anti-tumor agent, all cause cells to cease proliferation at levels of each agent which result in the displacement of zinc from metallothionein. These results are used to construct a model of zinc metabolism in which Zn metallothionein is a central, biochemically active form of zinc. The finding in a number of tumors other than Ehrlich ascites carcinoma of the existence of metal binding protein with characteristics similar to metallothionein suggests that the significantly elevated levels of metallothionein-like protein may be a general feature of many tumors and that it may play a vital role in rapidly proliferating tissue in general.
- OSTI ID:
- 5966091
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BIOLOGICAL FUNCTIONS
CADMIUM
CARCINOMAS
DISEASES
ELEMENTS
FUNCTIONS
GROWTH
INHIBITION
METABOLISM
METALLOPROTEINS
METALLOTHIONEIN
METALS
NEOPLASMS
ORGANIC COMPOUNDS
PROMOTERS
PROTEINS
STIMULATION
TUMOR PROMOTERS
ZINC