Copper hepatotoxicity attenuated by zinc

Conference · Fri May 01 04:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6119852

Schilsky, M; Blank, R; Stockert, R; Sternlieb, I; Scheinberg, I H

The manifestations of hepatocellular copper toxicity and the role of zinc in its prevention have been investigated. When incubated for 48 hrs in media to which increasing concentrations of Cu acetate are added, HepG2 cells exhibit reduced viability with an LD/sub 50/ of 750 uM. Morphology, cell membranes and mitochondria appeared to be normal after 1 hr exposure to 1000 uM Cu acetate, but progressive abnormalities were noted between 3 and 12 hrs. In the first hour of exposure to this concentration of copper, protein synthesis (/sup 35/S-methionine uptake into TCA precipitates) was reduced to 20% of control while transcription (/sup 3/H-uridine incorporation) increased to 139% of controls. Preincubation with 200 uM Zn acetate for 2 hr increased cellular survival and allowed protein synthesis to proceed at 80% of control levels during exposure to 1000 uM Cu acetate. /sup 67/Cu uptake was unaltered by incubation with up to 500 uM Zn acetate. SDS-PAGE of cellular proteins after treatment with 200 uM Zn produced a different banding pattern suggesting induction of specific proteins. Since the addition of 1000 uM Cu acetate to a wheat-germ-translation-system using B-globin mRNA reduced translation by 95%, they conclude from this and the foregoing data that copper inhibits protein synthesis at the level of translation and that zinc mitigates this inhibition in hepatocytes.

• Research Organization: Albert Einstein College of Medicine, Bronx, NY
• OSTI ID: 6119852
• Report Number(s): CONF-870644-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMAL CELLS
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOSYNTHESIS
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CELL MEMBRANES
COPPER
COPPER 67
COPPER ISOTOPES
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTROPHORESIS
ELEMENTS
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIGHT NUCLEI
LIPOTROPIC FACTORS
LIVER CELLS
MEMBRANES
METALS
METHIONINE
MITOCHONDRIA
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANOIDS
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RIBOSIDES
SOMATIC CELLS
SULFUR 35
SULFUR ISOTOPES
SYNTHESIS
TOXICITY
TRACER TECHNIQUES
TRANSITION ELEMENTS
TRITIUM COMPOUNDS
URACILS
URIDINE
VIABILITY
ZINC