Induction of metallothionein synthesis in cultured human trophoblasts by cadmium and zinc
Journal Article
·
· J. Toxicol. Environ. Health; (United States)
A system of primary cultures of human chorionic trophoblasts has been used for studying the effects of heavy metals on human reproductive tissue. Using this system, changes in cellular concentration of metallothionein (MT) in response to exposure to Cd or Zn were determined. Trophoblasts were isolated from term chorion laeve, grown in RPMI-1640 medium, and exposed to Cd or Zn. Cellular content of MT was measured using the Cd/heme radioassay. MT increased in concentration, and time-dependent manner after exposure to either metal. Cd increased the content of MT in trophoblasts at concentrations as low as 0.5 ..mu..M during a 24-h exposure. Moreover, extending exposure to Cd(2 ..mu..M) to 72 h resulted in a 3-4 fold increase in the concentration of MT. On a molar basis, Zn was not as potent a stimulus for MT synthesis as Cd, and required a concentration of 2.5 ..mu..M to increase the concentration of MT over a 24-h period. However, a 48- or 72-h exposure to Zn (10 ..mu..M) increased concentrations of MT nearly 8-fold over control values. Simultaneous exposure to Cd (2 ..mu..M) and inhibitors of protein synthesis, cycloheximide and actinomycin D, prevented the typical increase in MT concentration, suggesting that the metals act to increase the synthesis of MT. In another series of experiments, trophoblasts were exposed to Cd (2 ..mu..M) for 24 h, after which the cells were challenged with cytotoxic concentrations of Cd. Cells pretreated with Cd and then challenged with toxic concentrations of Cd had higher levels of MT and showed less toxicity, as indicated by leakage of lactic dehydrogenase. These results suggest that MT serves to sequester the metals in trophoblasts and reduce the toxicity of heavy metals. 34 references, 8 figures, 1 table.
- Research Organization:
- Univ. of Kansas Medical Center, Kansas City
- OSTI ID:
- 5885227
- Journal Information:
- J. Toxicol. Environ. Health; (United States), Journal Name: J. Toxicol. Environ. Health; (United States) Vol. 14:2-3; ISSN JTEHD
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACTINOMYCIN
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
CADMIUM
CELL CULTURES
CYCLOHEXIMIDE
DRUGS
ELEMENTS
EMBRYONIC CELLS
FUNCTIONS
FUNGICIDES
MAMMALS
MAN
METALLOPROTEINS
METALLOTHIONEIN
METALS
ORGANIC COMPOUNDS
PESTICIDES
PRIMATES
PROTEINS
RADIOASSAY
STIMULATION
SYNTHESIS
TIME DEPENDENCE
TOXICITY
VARIATIONS
VERTEBRATES
ZINC
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACTINOMYCIN
ANIMAL CELLS
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTIMITOTIC DRUGS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
CADMIUM
CELL CULTURES
CYCLOHEXIMIDE
DRUGS
ELEMENTS
EMBRYONIC CELLS
FUNCTIONS
FUNGICIDES
MAMMALS
MAN
METALLOPROTEINS
METALLOTHIONEIN
METALS
ORGANIC COMPOUNDS
PESTICIDES
PRIMATES
PROTEINS
RADIOASSAY
STIMULATION
SYNTHESIS
TIME DEPENDENCE
TOXICITY
VARIATIONS
VERTEBRATES
ZINC