42 research outputs found
Biological mechanisms of invasion and metastasis
The process of tumor invasion and metastasis is a complex cascade of events that include the following series of steps: release of neoplastic cells from the primary tumor, movement of tumor cells into the lymphatic or vasculature and arrest of the tumor cells in distant sites- biological mechanisms involve
Biological targets of cholinergic pesticides and possible use of alternative models for toxicity testing
The use of protection plant products for the control of pests in agriculture should be accompanied by a clear understanding of possible damages to human and environmental health. The mechanisms of action and the affects on developing organisms exerted by acute and chronic exposure to the main classes of cholinergic pesticides are reviewed
Apoptosis as a specific biomarker of diazinon toxicity in NTera2-D1 cells.
The NTera2/D1 (NT2) cell line, which was derived from a human teratocarcinoma, exhibits properties that are characteristics of a committed neuronal precursor at an early stage of differentiation. Its property to express a whole set of molecules related to the cholinergic neurotransmission system, including active acetylcholinesterase (AChE, EC 3.1.1.7) makes it a good alternative model for testing the effects of neurotoxic compounds, such as organophosphorus (OP) insecticides, whose primary target is the inhibition of AChE activity.
Recent findings have elucidated the role of AChE in the modulation of apoptosis, but the mechanisms are still rather obscure.
NT2 cells exposed to the OP insecticide diazinon at concentrations ranging between 10(-4) and 10(-5) M showed a time-dependent enhancement of cell death. When exposed at 10(-6) M diazinon showed higher cell viability than control samples up to 72 h, followed by a decreasing phase. The cell death caused by the exposures showed a number of features characteristic of apoptosis, including membrane and mitochondria] potential changes. We suggest the hypothesis that such behaviour is due to a dynamic balance between activated and blocked acetylcholine receptors that in turn trigger electrical events and caspase cascad
Sea urchin development: an alternative model for mechanistic understanding of neurodevelopment and neurotoxicity
Echinoderm early developmental stages might supply a good tool for toxicity testing in different fields, ranging from environment to food contamination, and in full respect of the 3Rs objectives (reduction, refinement, and replacement of animal experiments) that will eventually lead to the replacement of high vertebrate animal testing in toxicology. Sea urchin is one of the few organismic models considered by the European Agency for Alternative models. Actually, sea urchin embryonic development has been studied for over a century, and the complex nets of intercellular communications leading to the different events are well known, as well the possibility for environmental molecules and their residuals to interfere with such communications, causing developmental anomalies. In particular, the main goal of toxicologists since several years has been to establish a correlation between the cell-to-cell communications occurring during different developmental events and the signals occurring during neurogenesis, with the aim to pursue a mechanistic understanding of these processes and their deviations caused by stressors from different sources
The sea urchin, a versatile model for eco-toxicity studies and ecological experimental research
Echinoderm early developmental stages represent a good tool for toxicity testing in different fields, ranging from environment to food contamination, and in full respect of the 3Rs objectives (Reduction, Refinement, Replacement of animal experiments), that will lead to the reduction of vertebrate use for toxicity testing. Further, sea urchins are key species in a wide range of marine habitats, as they are able to structure algal community. Experiments and observations aiming at the characterization of anthropogenic or climate changes effects on their settlement, population structure, feeding behaviour and reproductive condition, may be useful to describe future scenarios regarding the whole marine community. The present paper represents a short review of the possible applications of eco-toxicity bioassays using Paracentrotus lividus gametes and embryos. Further, examples of ecological researches, involving sea urchins, aiming at the definition of future scenarios will be preserved
EFFECTS OF 8-CI-cAMP ON CELL GROWTH, DIFFERENTIATION AND APOPTOSIS IN Y-79 RETINOBLASTOMA CELL LINE
The sea urchin, Paracentrotus lividus, as a model to investigate the onset of molecules immunologically related to the \u3b1-7 subunit of nicotinic receptors during embryonic and larval development.
Nicotinic acetylcholine receptors play a major role in the regulation of electrochemical synapses at neuromuscular junctions. During the early stages of Paracentrotus lividus development, the nicotinic receptor-like molecules are found and localized by use of the specific blocker, -bungarotoxin, and by \u3b1-7 subunit immunoreactivity. Both the methods identify and localize the nicotinic receptor-like molecules at the sites where active changes in ionic intracellular concentration take place. These are well known to lead either fertilization, sperm propulsion or co-ordinated ciliary movement. After neural differentiation, immunoreactivity for the \u3b1-7 subunit is localized mainly in ganglia, ectoderm ciliary bands and in the motile cells forming the gut wall. Both \u3b1-bungarotoxin binding sites and \u3b1-7 subunits are also localized at the cells linked to the skeletal rods, performing the small movements which drive the swimming direction in the water column. The localization of these molecules paves the way to a speculation on their function and possible role in neurogenesis as well as neurodegeneration
Dose-dependent effects of chlorpyriphos, an organophosphate pesticide, on metamorphosis of the sea urchin, Paracentrotus lividus
The effect of exposures to the insecticide
chlorpyrifos on the larval stages of Paracentrotus lividus
(Echinodermata, Euechinoidea) up to metamorphosis was
investigated with the aim to identify novel risk biomarkers
and a new promising model for toxicity tests. The planktonic
sea urchin larvae have the ability to undergo a variable
exploratory period, up to the choice of a suitable
substrate for adult benthonic life. The juvenile bud (called
rudiment) is built inside the larval body that, on environmental
cues represented by a variety of signal molecules, is
reabsorbed by apoptosis and releases the juvenile on the
substrate. In this dialogue between larvae and environment,
contaminants interfere with the signals reception, and may
alter in dose-dependent way the correct regulation of
environment-larva-rudiment interaction. Such interaction is
shown by larval plasticity, i.e. the ability of the larva to
change body proportions according to the environmental
conditions. When exposed to low doses of chlorpyriphos
(10-7 to 10-10 M) since 2-days after fertilization, the larvae
showed altered size and shape, but all reached the
metamorphosis at the same time as controls, and in the
same percentage. Exposures to high concentrations such as
10-4 to 10-6 M since 2-days after fertilization did not
allow larval growth and differentiation. Exposures at later
stages caused reabsorption of larval structures within a few
hours and precocious release of the immature rudiments,
followed by death of the juveniles. Although the mechanism
of chlorpyriphos toxicity in sea urchin larvae is still
rather unclear, the measurable stress biomarkers can constitute the basis for new toxicity tests
Antiapoptotic and antigenotoxic effects of N-acetylcysteine in human cells of endothelial origin
N-Acetylcysteine (NAC) is a drug bearing multiple preventive properties that can inhibit genotoxicity and carcinogenicity. NAC also inhibits invasion and metastasis of malignant cells, as well as tumor take. We recently demonstrated the effects of NAC on Kaposi's sal coma cells supernatant-induced invasion in vitro and angiogenesis in vivo. Many anticancer agents act through cytotoxicity of rapidly proliferating cells and several antineoplastic drugs induce apoptosis of cancel cells. Since endothelial cells are the target for the inhibition of angiogenesis, we wanted to verify that NAC, while inhibiting tumor vascularization and endothelial cell invasion would not induce endothelial cell apoptosis. We tested the ability of NAC to modulate apoptosis and cytogenetic damage in vitro and to promote differentiation on a reconstituted basement membrane (matrigel) in two endothelial cell lines (EAhy926 and HUVE). Treatment with NAC protected endothelial cells from TGF-beta -induced apoptosis and paraquat-induced cytogenetic damage. Therefore, NAC acts as an antiangiogenic agent and, at the same time, appeals to pl event apoptosis and oxygen-related genotoxicity in endothelial cells