Relationship between zinc and neurotransmitters released into the amygdalar extracellular space.

On the basis of the evidence that vesicular zinc may be essential to the functions of the amygdala, the movement and action of actively functioning zinc in synapses in the amygdala of rats were studied using in vivo microdialysis. The increase of (65)Zn release into the amygdalar extracellular space during stimulation with high K(+) was inhibited by the addition of 1 microM tetrodotoxin. High-K(+)-induced (65)Zn release was not observed in the substantia nigra, in which zinc-containing glutamatergic neuron terminals are assumed not to exist. The amount of (65)Zn released into the amygdalar extracellular space during stimulation with high K(+) was correlated with that of glutamate. These results suggest that zinc may be concurrently released with glutamate from the neuron terminals in the amygdala and that zinc may cooperate with glutamate in excitatory neurotransmission. When the amygdala was perfused with 10 microM calcium-ethylenediamine tetraacetic acid (CaEDTA) to chelate zinc in the extracellular space, the levels of glutamate in the extracellular space were not appreciably influenced, whereas those of gamma-aminobutyric acid (GABA) were remarkably increased. It is likely that vesicular zinc modulates GABA release in the amygdala. The modulation of GABAergic neuron activity by zinc may be important for the functions of the amygdala.

Age-dependent variation of zinc-65 metabolism in LACA mice.

Mice were gavaged with zinc-65 solution, 8.6-19.3 kBq per mouse, and the whole-body retention and organ content of zinc-65 were measured at different times after administration. The age-dependence of the fractional absorption of zinc-65 from the gastrointestinal tract (f1), the endogenous faecal excretion fraction of zinc-65 (EFEF), tissue distribution and whole-body retention were determined. The f1 values obtained were 0.86 +/- 0.15, 0.64 +/- 0.11, 0.52 +/- 0.07 and 0.39 +/- 0.02 in suckling, adolescent, young adult and older mice, respectively. The EFEF values determined were 0.083 +/- 0.008, 0.099 +/- 0.004, 0.122 +/- 0.018 and 0.144 +/- 0.005 of intraperitoneally injected zinc-65 in suckling, adolescent, young adult and older mice at administration. Zinc-65 mainly distributed in the liver, muscle, lung, kidneys and bone. In some tissues, there was an inverse relationship between the relative content of gavaged zinc-65 and the animal's age at administration. The whole-body biological half-lives of zinc-65 increased with animal age. The influence of the age-dependent variation of zinc-65 metabolism on internal dose and on radiation protection is discussed.

Cytotoxicity, genotoxicity and intracellular distribution of the Auger electron emitter (65)Zn in two human cell lines.

Cell survival, induction of apoptosis, and micronucleus formation have been examined in non-transformed human amnion fluid fibroblast-like (AFFL) cells and in a human squameous cell carcinoma (SCL-II) cell line after exposure to the Auger electron emitter (65)Zn and after external low-LET radiation. Cellular uptake and subcellular distribution of (65)Zn(2+) were studied in vitro and the absorbed radiation dose was calculated applying analytical dosimetry models. Auger electrons generated during decay of (65)Zn induced a prominent decrease in cell survival and increased the levels of apoptotic as well as micronucleated cells when compared to external low-LET irradiation. Relative biological effectiveness has been determined for cell survival (RBE approximately 4), micronucleus formation (RBE approximately 2) and apoptosis induction (RBE approximately 5-8) in SCL-II cells and for micronucleus formation (RBE approximately 4-5) and apoptosis induction (RBE approximately 6-10) in AFFL cells, respectively. This demonstrates a general enhanced biological effectiveness of (65)Zn in both investigated cell lines when compared to external low-LET radiation. The distribution pattern of intracellular Zn(2+) was found to be non-uniform, showing enhanced amounts of Zn(2+) in the perinuclear region and low amounts inside the cell nucleus, suggesting a major energy deposition close to the nuclear envelope.

Apoptosis induction and micronucleus formation after exposure to the Auger electron emitter zinc-65 in a human cell line.

Induction of apoptosis and micronucleus formation has been studied in a transformed human squamous cell carcinoma cell line (SCL-II) after exposure to the Auger electron emitter Zinc-65 (65Zn) and after external low-LET radiation. Exposure to non-radioactive Zn and unirradiated cells served as controls. Studies on the cellular uptake of 65Zn2+ have been carried out in vitro and conventional dosimetric models have been applied to derive the absorbed radiation dose. Auger electrons, generated during decay of 65Zn2+, are strong inducers of micronuclei as well as of apoptosis, in comparison to external low-LET irradiation. The relative biological effectiveness has been determined and was found to be in the range of 1.2-2.7 for the two investigated biological endpoints, depending on which mathematical model for describing the dose-effect curves was used. A non-uniform distribution of intracellular Zn2 + was observed, showing a strong signal in the perinuclear region. We conclude that separate radiation weighting factors for Auger electrons should be established depending on the nuclide and its ability to interact with the DNA (e.g. 65Zn by Zinc-finger proteins).