Antonella Russo | University of Catania (original) (raw)
Papers by Antonella Russo
Experimental brain research, Jan 8, 2015
Previous studies performed in rats showed that the whisker-pad motor innervation involves not onl... more Previous studies performed in rats showed that the whisker-pad motor innervation involves not only the facial nerve, but also some hypoglossal neurons whose axons travel within the trigeminal infraorbital nerve (ION) and target the extrinsic muscles surrounding the whisker-pad macrovibrissae. Furthermore, the electrical stimulation of the ION induced an increase in the EMG activity of these muscles, while the hypoglossal nucleus stimulation elicited evoked potentials and single motor unit responses. However, the existence of a neural network able to involve the XIIth nucleus in macrovibrissae whisking control was totally unknown until now. Since other recent experiments demonstrated that: (1) the mesencephalic trigeminal nucleus (Me5) neurons respond to both spontaneous and artificial movements of macrovibrissae, and (2) the Me5 peripheral terminals provide a monosynaptic sensory innervation to the macrovibrissae, the present study was aimed at analyzing a possible role of the Me5 n...
Hepatology, 1996
Drug-or alcohol-induced liver diseases were also excluded on the Address reprint requests to: Mas... more Drug-or alcohol-induced liver diseases were also excluded on the Address reprint requests to: Massimo Colombo, M.D., Institute of Internal Medicine, basis of the patient's history and liver histology. All patients were
Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis, Feb 28, 1987
(C57B1/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons (fr... more (C57B1/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons (from 0.11 to 0.72 Gy) or 250 kV X-rays (from 0.25 to 3 Gy) and sacrificed 5 days later. Chromosome preparations of secondary spermatocytes, irradiated at the stage of pachytene, were analysed and the incidence of hyper-haploidies and chromosome fragments was recorded. Data on numerical aberrations were fitted by highly significant linear relationships for both types of radiation. A relative biological effectiveness (RBE) value of 5.65 was estimated by the ratio between the slopes of the two regression lines. The same linear fitting was applied to frequencies of cells with fragments, even if in this case other types of functions could not be excluded. An RBE value was estimated in the same way as for numerical aberrations and yielded a comparable figure of 5.23. A significant correlation was also found between the incidence of numerical and structural aberrations, which points to the chromosome itself as the prevalent target for radiation-induced non-disjunction (ND). In addition, the highly significant linearity of the dose-effect relationship observed for the induction of aneuploidies suggests, as the simplest hypothesis, a single-hit mechanism of radiation action, possibly through pre-non-disjunctional damage to the centromeric region, rather than an indirect induction of segregational difficulties after primarily induced chromatid interchanges.
Environmental and molecular mutagenesis, Jan 19, 2015
The Organisation for Economic Co-operation and Development (OECD) has launched the Adverse Outcom... more The Organisation for Economic Co-operation and Development (OECD) has launched the Adverse Outcome Pathway (AOP) Programme to advance knowledge of pathways of toxicity and improve the use of mechanistic information in risk assessment. An AOP links a molecular initiating event (MIE) to an adverse outcome (AO) through intermediate key events (KE). Here, we present the scientific evidence in support of an AOP whereby chemicals that bind to tubulin cause microtubule depolymerization resulting in spindle disorganization followed by altered chromosome alignment and segregation and the generation of aneuploidy in female germ cells, ultimately leading to aneuploidy in the offspring. Aneuploidy, an abnormal number of chromosomes that is not an exact multiple of the haploid number, is a well-known cause of human disease and represents a major cause of infertility, pregnancy failure, and serious genetic disorders in the offspring. Among chemicals that induce aneuploidy in female germ cells, a ...
Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia
Catecholamines are neurotransmitters involved in the regulation of testicular function and they a... more Catecholamines are neurotransmitters involved in the regulation of testicular function and they activate the Leydig cell receptors. To assess whether the two key-enzymes involved in the synthesis of catecholamines are present in human testis we examined the expression of Tirosine Hydroxylase (TH) and Dopamine-beta-Hydroxylase (DBH) antigens by immunoperoxidase and immunofluorescence techniques. Sections from testicular biopsies of adult and infant patients were processed by two antibodies. In all specimens Leydig cells stain positively. Differences in the staining positivity among single Leydig cells and among cell groups as well as among Leydig cells from different patients were noted. In some of the reactions a small number of Leydig cells was negative. Most of the immunoreactivity is evenly distributed within the cytoplasm of the Leydig cells. We suggest that the heterogeneous expression among Leydig cells could be correlated to their different metabolic activity. Our observation...
Pflügers Archiv : European journal of physiology, 2003
Natural olfactory stimulation with amyl acetate significantly modulates the electrical activity o... more Natural olfactory stimulation with amyl acetate significantly modulates the electrical activity of hypoglossal neurons and the electromyographic responses of the tongue musculature. The aim of the present study was to identify and characterize, using neuroanatomical and neurophysiological approaches, the pathways involved in the transmission of the olfactory information to the hypoglossal nucleus (XIIn). The neuroanatomical findings provided the initial demonstration that olfactory information is conveyed from the olfactory bulb to the hypoglossal nucleus via the interpeduncular nucleus (IPn) by both fast disynaptic and different polysynaptic pathways. The latter, in particular, involve many of the brain structures that process olfactory information. The electrophysiological studies demonstrated that the IPn neurons respond with a variety of patterns to natural stimulation of the olfactory receptors, thus supporting the hypothesis that the IPn is a crucial relay station for the elab...
Neuroscience Research
Tissue transglutaminase (TG2), a multifunctional enzyme implicated in cellular proliferation and ... more Tissue transglutaminase (TG2), a multifunctional enzyme implicated in cellular proliferation and differentiation processes, plays a modulatory role in the cell response to stressors. Herein, we used olfactory ensheathing cells (OECs), representing an unusual population of glial cells to promote axonal regeneration and to provide trophic support, as well as to assess whether the effect of some Growth Factors (GFs), NGF, bFGF or GDNF, on TG2 overexpression induced by stress conditions, such as glutamate or lipopolysaccaride (LPS). Glial Fibrillary Acidic Protein (GFAP) and vimentin were used as markers of astroglial differentiation and cytoskeleton component, respectively. Glutamate or LPS treatment induced a particular increase of TG2 expression. A pre-treatment of the cells with the GFs restored the levels of the protein to that of untreated ones. Our results demonstrate that the treatment of OECs with the GFs was able to restore the OECs oxidative status as modified by stress, also...
Journal of thrombosis and haemostasis : JTH, Jan 6, 2015
Platelet secretion is critical to development of acute thrombotic occlusion. Platelet dense granu... more Platelet secretion is critical to development of acute thrombotic occlusion. Platelet dense granules contain a variety of important hemostatically active substances. Nevertheless, biogenesis of platelet granules is poorly understood. SGK1 has been shown to be highly expressed in platelets and megakaryocytes, but its role in the regulation of platelet granule biogenesis and its impact on thrombosis has not been investigated so far. Electron microscopy analysis of platelet ultrastructure revealed significant reduction in number and packing of dense granules in platelets lacking SGK1 (sgk1(-/-) ). In sgk1(-/-) platelets serotonin content was significantly reduced and activation-dependent secretion of ATP, serotonin and CD63 significantly impaired. In vivo adhesion after carotis ligation was significantly decreased in platelets lacking SGK1 and occlusive thrombus formation after FeCl3 -induced vascular injury was significantly diminished in sgk1(-/-) mice. Transcript levels and protein ...
Environmental and molecular mutagenesis, Jan 18, 2015
Genomic instability leads to a wide spectrum of genetic changes, including single nucleotide muta... more Genomic instability leads to a wide spectrum of genetic changes, including single nucleotide mutations, structural chromosome alterations, and numerical chromosome changes. The accepted view on how these events are generated predicts that separate cellular mechanisms and genetic events explain the occurrence of these types of genetic variation. Recently, new findings have shed light on the complexity of the mechanisms leading to structural and numerical chromosome aberrations, their intertwining pathways, and their dynamic evolution, in somatic as well as in germ cells. In this review, we present a critical analysis of these recent discoveries in this area, with the aim to contribute to a deeper knowledge of the molecular networks leading to adverse outcomes in humans following exposure to environmental factors. The review illustrates how several technological advances, including DNA sequencing methods, bioinformatics, and live-cell imaging approaches, have contributed to produce a ...
Behavioral and brain functions : BBF, Jan 7, 2005
Different findings indicate that rostral ventrolateral reticular nucleus (RVL) is neuronal substr... more Different findings indicate that rostral ventrolateral reticular nucleus (RVL) is neuronal substrate of integration and regulation of the cardiovascular functions. Some efferent RVL neurons project to the thoraco-lumbar spinal cord and excite preganglionic sympathetic neurons, to the spinal phrenic motor neurons involved in inspiratory function and increase the activity of vasoconstrictor fibres innervating blood vessels in the skin and skeletal muscle. Our study was aimed at revealing presence of neurons within RVL supplying branching collateral input to the medial preoptic area (MPA) and to the lumbo-sacral spinal cord (SC-L) in the rat. All animal experiments were carried out in accordance with current institutional guidelines for the care and use of experimental animals. We have employed double fluorescent-labelling procedure: the projections were defined by injections of two retrograde tracers: Rhodamine Labelled Bead (RBL) and Fluoro Gold (FG) in the MPA and SC-L, respectively...
Mutation research, Jan 16, 1998
The frequency of micronuclei induced in mouse meiotic cells after exposure to 1,3-butadiene has b... more The frequency of micronuclei induced in mouse meiotic cells after exposure to 1,3-butadiene has been evaluated in early spermatids. Germ cells were isolated from mice exposed to three butadiene concentrations (130, 250 and 500 ppm), at time intervals allowing to evaluate effects induced in late spermatocytes or at the stage of prelepotene/differentiating spermatogonia. The characterization of the origin of micronuclei, by simultaneous detection of centromeric and telomeric sequences, was also done on spermatid preparations from the 250 ppm concentration. The same analysis was carried out on a group of mice treated with the major butadiene metabolite, 1,2,3,4-diepoxybutane. The results obtained indicate a weak clastogenic effect of butadiene to premeiotic germ cells in the mouse.
Mutation research, Jan 16, 1998
The effect of different 1,3-butadiene (BD) inhalation doses, 130, 250, and 500 ppm, on somatic ce... more The effect of different 1,3-butadiene (BD) inhalation doses, 130, 250, and 500 ppm, on somatic cells of mice was studied. Two different cell populations with diverse replicative and differentiative activities, namely splenocytes and peripheral blood reticulocytes, were examined and micronucleus (MN) frequencies were estimated. In splenocytes, different postinhalation time intervals were studied with regard to MN induction and characterisation. BD was found to be clastogenic by inducing increased micronucleus frequencies in both cell compartments and also to induce cytotoxicity at the highest level of exposure. In mouse splenocytes, BD has also shown a weak aneugenic effect at a short time interval after the exposure. Postinhalation time influences the induction of chromosome damage in stimulated splenocytes treated in vivo, since MN frequency decreases with time; in addition, BD has shown its aneugenic and cytotoxic potential only at 2 days after exposure.
Mutation research, 1993
The frequency of sister-chromatid exchanges (SCE) was evaluated in mouse bone marrow cells at dif... more The frequency of sister-chromatid exchanges (SCE) was evaluated in mouse bone marrow cells at different time intervals (from 19 h to 10 days) after treatment i.p. with mitomycin C (MMC; 1 and 2 mg/kg body weight). Significantly higher frequencies of SCE were found during the first week after treatment, at both doses tested. This result confirms that chromosomal lesions induced by MMC in the mouse may persist in bone marrow cells, in agreement with previous evidence based on chromosomal aberration analysis in the same cell population. In addition, the observation of a unimodal distribution of SCE/cell frequencies at each time tested indicates that the bone marrow cell population on the whole is affected by increased SCE frequency, i.e., that persistent chromosomal lesions may be transmitted along with cell proliferation.
Mutation research, 1983
(C57B1/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons (fr... more (C57B1/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons (from 0.11 to 0.72 Gy) or 250 kV X-rays (from 0.25 to 3 Gy) and sacrificed 5 days later. Chromosome preparations of secondary spermatocytes, irradiated at the stage of pachytene, were analysed and the incidence of hyper-haploidies and chromosome fragments was recorded. Data on numerical aberrations were fitted by highly significant linear relationships for both types of radiation. A relative biological effectiveness (RBE) value of 5.65 was estimated by the ratio between the slopes of the two regression lines. The same linear fitting was applied to frequencies of cells with fragments, even if in this case other types of functions could not be excluded. An RBE value was estimated in the same way as for numerical aberrations and yielded a comparable figure of 5.23. A significant correlation was also found between the incidence of numerical and structural aberrations, which points to the chromosome itself as the prevalent target for radiation-induced non-disjunction (ND). In addition, the highly significant linearity of the dose-effect relationship observed for the induction of aneuploidies suggests, as the simplest hypothesis, a single-hit mechanism of radiation action, possibly through pre-non-disjunctional damage to the centromeric region, rather than an indirect induction of segregational difficulties after primarily induced chromatid interchanges.
Bollettino della Società italiana di biologia sperimentale
Environmental Mutagenesis, 1984
The effects of chloral hydrate (CH), an in vivo metabolite of trichloroethylene, have been evalua... more The effects of chloral hydrate (CH), an in vivo metabolite of trichloroethylene, have been evaluated by cytogenetic observations of mouse secondary sperniatocytes after ip treatment with 82.7, 165.4, or 413.5 nig/kg bw. Hyper-haploid metaphases have been scored to determine whether previous observations in various nonmammalian organisms about an effect of this drug on the mitotic spindle could be confirmed in mice.
Cellular Physiology and Biochemistry, 2014
This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCo... more This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Journal of Behavioral and Brain Science, 2012
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1998
A summary of the results of the studies conducted in the EU Project "Multi-endpoint anal... more A summary of the results of the studies conducted in the EU Project "Multi-endpoint analysis of genetic damage induced by 1,3-butadiene and its major metabolites in somatic and germ cells of mice, rats and man" is presented. Results of the project are summarized on the detection of DNA and hemoglobin adducts, on the cytotoxic and clastogenic effects in somatic and germinal cells of mice and rats, on the induction of somatic mutations at the hprt locus of experimental rodents and occupationally exposed workers, on the induction of dominant lethal mutations in mice and rats, and on heritable translocations induced in mice, after exposure to butadiene (BD) or its major metabolites, butadiene monoepoxide (BMO), diepoxybutane (DEB) and butadiene diolepoxide (BDE). The primary goal of this project was to collect experimental data on the genetic effects of BD in order to estimate the germ cell genetic risk to humans of exposure to BD. To achieve this, the butadiene exposure are based on data for heritable translocations and bone marrow micronuclei induced in mice and chromosome aberrations observed in lymphocytes of exposed workers. A doubling dose for heritable translocations in human germ cells of 4900 ppm/h is estimated, which, assuming cumulative BD exposure over the sensitive period of spermatogenesis, corresponds to 5-6 weeks of continuous exposure at the workplace to 20-25 ppm. Alternatively, the rate of heritable translocation induction per ppm/h of BD exposure is estimated to be approximately 0.8 per million live born, compared to a spontaneous incidence of balanced translocations in humans of approximately 800 per million live born. These estimates have large confidence intervals and are only intended to indicate orders of magnitude of human genetic risk. These risk estimates are based on data from germ cells of BD-exposed male mice. The demonstration that clastogenic damage was induced by DEB in preovulatory oocytes at doses which were not ovotoxic implies that additional studies on the response of mammalian female germ cells to BD and its metabolites are needed. The basic assumption of the above genetic risk estimates is that experimental mouse data obtained after BD exposure can be extrapolated to humans. Several points exist in the present report and in the literature which contradict this assumption: (1) the level of BMO-hemoglobin adducts was significantly elevated in BD-exposed workers; however, it was considerably lower than would have been predicted from comparable rat and mouse exposures; (2) the concentrations of the metabolites DEB and BMO were significantly higher in mouse than in rat blood after BD exposure. Thus, while metabolism of BD is qualitatively similar in the two species, it is quantitatively different; (3) no increase of HPRT mutations was shown in 19 workers exposed on average to 1.8 ppm of BD, while in a different population of workers from a US plant exposed on average to 3.5 ppm of BD, a significant increase of HPRT variants was detected; and (4) data from cancer bioassays and cancer epidemiology suggest that rat is a more appropriate model than mouse for human cancer risk from BD exposure. However, the dominant lethal study in rats gave a negative result. At present, we do not know which BD metabolite(s) may be responsible for the genetic effects even though the bifunctional alkylating agent DEB is the most likely candidate for the induction of clastogenic events. Unfortunately, methods to measure DEB adducts in hemoglobin or DNA are only presently being developed. Despite these several uncertainties the use of the mouse genetic data is regarded as a justifiable and conservative approach to human genetic risk estimation given the considerable heterogeneity observed in the biotransformation of BD in humans.
Experimental brain research, Jan 8, 2015
Previous studies performed in rats showed that the whisker-pad motor innervation involves not onl... more Previous studies performed in rats showed that the whisker-pad motor innervation involves not only the facial nerve, but also some hypoglossal neurons whose axons travel within the trigeminal infraorbital nerve (ION) and target the extrinsic muscles surrounding the whisker-pad macrovibrissae. Furthermore, the electrical stimulation of the ION induced an increase in the EMG activity of these muscles, while the hypoglossal nucleus stimulation elicited evoked potentials and single motor unit responses. However, the existence of a neural network able to involve the XIIth nucleus in macrovibrissae whisking control was totally unknown until now. Since other recent experiments demonstrated that: (1) the mesencephalic trigeminal nucleus (Me5) neurons respond to both spontaneous and artificial movements of macrovibrissae, and (2) the Me5 peripheral terminals provide a monosynaptic sensory innervation to the macrovibrissae, the present study was aimed at analyzing a possible role of the Me5 n...
Hepatology, 1996
Drug-or alcohol-induced liver diseases were also excluded on the Address reprint requests to: Mas... more Drug-or alcohol-induced liver diseases were also excluded on the Address reprint requests to: Massimo Colombo, M.D., Institute of Internal Medicine, basis of the patient's history and liver histology. All patients were
Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis, Feb 28, 1987
(C57B1/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons (fr... more (C57B1/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons (from 0.11 to 0.72 Gy) or 250 kV X-rays (from 0.25 to 3 Gy) and sacrificed 5 days later. Chromosome preparations of secondary spermatocytes, irradiated at the stage of pachytene, were analysed and the incidence of hyper-haploidies and chromosome fragments was recorded. Data on numerical aberrations were fitted by highly significant linear relationships for both types of radiation. A relative biological effectiveness (RBE) value of 5.65 was estimated by the ratio between the slopes of the two regression lines. The same linear fitting was applied to frequencies of cells with fragments, even if in this case other types of functions could not be excluded. An RBE value was estimated in the same way as for numerical aberrations and yielded a comparable figure of 5.23. A significant correlation was also found between the incidence of numerical and structural aberrations, which points to the chromosome itself as the prevalent target for radiation-induced non-disjunction (ND). In addition, the highly significant linearity of the dose-effect relationship observed for the induction of aneuploidies suggests, as the simplest hypothesis, a single-hit mechanism of radiation action, possibly through pre-non-disjunctional damage to the centromeric region, rather than an indirect induction of segregational difficulties after primarily induced chromatid interchanges.
Environmental and molecular mutagenesis, Jan 19, 2015
The Organisation for Economic Co-operation and Development (OECD) has launched the Adverse Outcom... more The Organisation for Economic Co-operation and Development (OECD) has launched the Adverse Outcome Pathway (AOP) Programme to advance knowledge of pathways of toxicity and improve the use of mechanistic information in risk assessment. An AOP links a molecular initiating event (MIE) to an adverse outcome (AO) through intermediate key events (KE). Here, we present the scientific evidence in support of an AOP whereby chemicals that bind to tubulin cause microtubule depolymerization resulting in spindle disorganization followed by altered chromosome alignment and segregation and the generation of aneuploidy in female germ cells, ultimately leading to aneuploidy in the offspring. Aneuploidy, an abnormal number of chromosomes that is not an exact multiple of the haploid number, is a well-known cause of human disease and represents a major cause of infertility, pregnancy failure, and serious genetic disorders in the offspring. Among chemicals that induce aneuploidy in female germ cells, a ...
Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia
Catecholamines are neurotransmitters involved in the regulation of testicular function and they a... more Catecholamines are neurotransmitters involved in the regulation of testicular function and they activate the Leydig cell receptors. To assess whether the two key-enzymes involved in the synthesis of catecholamines are present in human testis we examined the expression of Tirosine Hydroxylase (TH) and Dopamine-beta-Hydroxylase (DBH) antigens by immunoperoxidase and immunofluorescence techniques. Sections from testicular biopsies of adult and infant patients were processed by two antibodies. In all specimens Leydig cells stain positively. Differences in the staining positivity among single Leydig cells and among cell groups as well as among Leydig cells from different patients were noted. In some of the reactions a small number of Leydig cells was negative. Most of the immunoreactivity is evenly distributed within the cytoplasm of the Leydig cells. We suggest that the heterogeneous expression among Leydig cells could be correlated to their different metabolic activity. Our observation...
Pflügers Archiv : European journal of physiology, 2003
Natural olfactory stimulation with amyl acetate significantly modulates the electrical activity o... more Natural olfactory stimulation with amyl acetate significantly modulates the electrical activity of hypoglossal neurons and the electromyographic responses of the tongue musculature. The aim of the present study was to identify and characterize, using neuroanatomical and neurophysiological approaches, the pathways involved in the transmission of the olfactory information to the hypoglossal nucleus (XIIn). The neuroanatomical findings provided the initial demonstration that olfactory information is conveyed from the olfactory bulb to the hypoglossal nucleus via the interpeduncular nucleus (IPn) by both fast disynaptic and different polysynaptic pathways. The latter, in particular, involve many of the brain structures that process olfactory information. The electrophysiological studies demonstrated that the IPn neurons respond with a variety of patterns to natural stimulation of the olfactory receptors, thus supporting the hypothesis that the IPn is a crucial relay station for the elab...
Neuroscience Research
Tissue transglutaminase (TG2), a multifunctional enzyme implicated in cellular proliferation and ... more Tissue transglutaminase (TG2), a multifunctional enzyme implicated in cellular proliferation and differentiation processes, plays a modulatory role in the cell response to stressors. Herein, we used olfactory ensheathing cells (OECs), representing an unusual population of glial cells to promote axonal regeneration and to provide trophic support, as well as to assess whether the effect of some Growth Factors (GFs), NGF, bFGF or GDNF, on TG2 overexpression induced by stress conditions, such as glutamate or lipopolysaccaride (LPS). Glial Fibrillary Acidic Protein (GFAP) and vimentin were used as markers of astroglial differentiation and cytoskeleton component, respectively. Glutamate or LPS treatment induced a particular increase of TG2 expression. A pre-treatment of the cells with the GFs restored the levels of the protein to that of untreated ones. Our results demonstrate that the treatment of OECs with the GFs was able to restore the OECs oxidative status as modified by stress, also...
Journal of thrombosis and haemostasis : JTH, Jan 6, 2015
Platelet secretion is critical to development of acute thrombotic occlusion. Platelet dense granu... more Platelet secretion is critical to development of acute thrombotic occlusion. Platelet dense granules contain a variety of important hemostatically active substances. Nevertheless, biogenesis of platelet granules is poorly understood. SGK1 has been shown to be highly expressed in platelets and megakaryocytes, but its role in the regulation of platelet granule biogenesis and its impact on thrombosis has not been investigated so far. Electron microscopy analysis of platelet ultrastructure revealed significant reduction in number and packing of dense granules in platelets lacking SGK1 (sgk1(-/-) ). In sgk1(-/-) platelets serotonin content was significantly reduced and activation-dependent secretion of ATP, serotonin and CD63 significantly impaired. In vivo adhesion after carotis ligation was significantly decreased in platelets lacking SGK1 and occlusive thrombus formation after FeCl3 -induced vascular injury was significantly diminished in sgk1(-/-) mice. Transcript levels and protein ...
Environmental and molecular mutagenesis, Jan 18, 2015
Genomic instability leads to a wide spectrum of genetic changes, including single nucleotide muta... more Genomic instability leads to a wide spectrum of genetic changes, including single nucleotide mutations, structural chromosome alterations, and numerical chromosome changes. The accepted view on how these events are generated predicts that separate cellular mechanisms and genetic events explain the occurrence of these types of genetic variation. Recently, new findings have shed light on the complexity of the mechanisms leading to structural and numerical chromosome aberrations, their intertwining pathways, and their dynamic evolution, in somatic as well as in germ cells. In this review, we present a critical analysis of these recent discoveries in this area, with the aim to contribute to a deeper knowledge of the molecular networks leading to adverse outcomes in humans following exposure to environmental factors. The review illustrates how several technological advances, including DNA sequencing methods, bioinformatics, and live-cell imaging approaches, have contributed to produce a ...
Behavioral and brain functions : BBF, Jan 7, 2005
Different findings indicate that rostral ventrolateral reticular nucleus (RVL) is neuronal substr... more Different findings indicate that rostral ventrolateral reticular nucleus (RVL) is neuronal substrate of integration and regulation of the cardiovascular functions. Some efferent RVL neurons project to the thoraco-lumbar spinal cord and excite preganglionic sympathetic neurons, to the spinal phrenic motor neurons involved in inspiratory function and increase the activity of vasoconstrictor fibres innervating blood vessels in the skin and skeletal muscle. Our study was aimed at revealing presence of neurons within RVL supplying branching collateral input to the medial preoptic area (MPA) and to the lumbo-sacral spinal cord (SC-L) in the rat. All animal experiments were carried out in accordance with current institutional guidelines for the care and use of experimental animals. We have employed double fluorescent-labelling procedure: the projections were defined by injections of two retrograde tracers: Rhodamine Labelled Bead (RBL) and Fluoro Gold (FG) in the MPA and SC-L, respectively...
Mutation research, Jan 16, 1998
The frequency of micronuclei induced in mouse meiotic cells after exposure to 1,3-butadiene has b... more The frequency of micronuclei induced in mouse meiotic cells after exposure to 1,3-butadiene has been evaluated in early spermatids. Germ cells were isolated from mice exposed to three butadiene concentrations (130, 250 and 500 ppm), at time intervals allowing to evaluate effects induced in late spermatocytes or at the stage of prelepotene/differentiating spermatogonia. The characterization of the origin of micronuclei, by simultaneous detection of centromeric and telomeric sequences, was also done on spermatid preparations from the 250 ppm concentration. The same analysis was carried out on a group of mice treated with the major butadiene metabolite, 1,2,3,4-diepoxybutane. The results obtained indicate a weak clastogenic effect of butadiene to premeiotic germ cells in the mouse.
Mutation research, Jan 16, 1998
The effect of different 1,3-butadiene (BD) inhalation doses, 130, 250, and 500 ppm, on somatic ce... more The effect of different 1,3-butadiene (BD) inhalation doses, 130, 250, and 500 ppm, on somatic cells of mice was studied. Two different cell populations with diverse replicative and differentiative activities, namely splenocytes and peripheral blood reticulocytes, were examined and micronucleus (MN) frequencies were estimated. In splenocytes, different postinhalation time intervals were studied with regard to MN induction and characterisation. BD was found to be clastogenic by inducing increased micronucleus frequencies in both cell compartments and also to induce cytotoxicity at the highest level of exposure. In mouse splenocytes, BD has also shown a weak aneugenic effect at a short time interval after the exposure. Postinhalation time influences the induction of chromosome damage in stimulated splenocytes treated in vivo, since MN frequency decreases with time; in addition, BD has shown its aneugenic and cytotoxic potential only at 2 days after exposure.
Mutation research, 1993
The frequency of sister-chromatid exchanges (SCE) was evaluated in mouse bone marrow cells at dif... more The frequency of sister-chromatid exchanges (SCE) was evaluated in mouse bone marrow cells at different time intervals (from 19 h to 10 days) after treatment i.p. with mitomycin C (MMC; 1 and 2 mg/kg body weight). Significantly higher frequencies of SCE were found during the first week after treatment, at both doses tested. This result confirms that chromosomal lesions induced by MMC in the mouse may persist in bone marrow cells, in agreement with previous evidence based on chromosomal aberration analysis in the same cell population. In addition, the observation of a unimodal distribution of SCE/cell frequencies at each time tested indicates that the bone marrow cell population on the whole is affected by increased SCE frequency, i.e., that persistent chromosomal lesions may be transmitted along with cell proliferation.
Mutation research, 1983
(C57B1/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons (fr... more (C57B1/Cne X C3H/Cne)F1 male mice were irradiated with single acute doses of 0.4 MeV neutrons (from 0.11 to 0.72 Gy) or 250 kV X-rays (from 0.25 to 3 Gy) and sacrificed 5 days later. Chromosome preparations of secondary spermatocytes, irradiated at the stage of pachytene, were analysed and the incidence of hyper-haploidies and chromosome fragments was recorded. Data on numerical aberrations were fitted by highly significant linear relationships for both types of radiation. A relative biological effectiveness (RBE) value of 5.65 was estimated by the ratio between the slopes of the two regression lines. The same linear fitting was applied to frequencies of cells with fragments, even if in this case other types of functions could not be excluded. An RBE value was estimated in the same way as for numerical aberrations and yielded a comparable figure of 5.23. A significant correlation was also found between the incidence of numerical and structural aberrations, which points to the chromosome itself as the prevalent target for radiation-induced non-disjunction (ND). In addition, the highly significant linearity of the dose-effect relationship observed for the induction of aneuploidies suggests, as the simplest hypothesis, a single-hit mechanism of radiation action, possibly through pre-non-disjunctional damage to the centromeric region, rather than an indirect induction of segregational difficulties after primarily induced chromatid interchanges.
Bollettino della Società italiana di biologia sperimentale
Environmental Mutagenesis, 1984
The effects of chloral hydrate (CH), an in vivo metabolite of trichloroethylene, have been evalua... more The effects of chloral hydrate (CH), an in vivo metabolite of trichloroethylene, have been evaluated by cytogenetic observations of mouse secondary sperniatocytes after ip treatment with 82.7, 165.4, or 413.5 nig/kg bw. Hyper-haploid metaphases have been scored to determine whether previous observations in various nonmammalian organisms about an effect of this drug on the mitotic spindle could be confirmed in mice.
Cellular Physiology and Biochemistry, 2014
This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCo... more This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Journal of Behavioral and Brain Science, 2012
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1998
A summary of the results of the studies conducted in the EU Project "Multi-endpoint anal... more A summary of the results of the studies conducted in the EU Project "Multi-endpoint analysis of genetic damage induced by 1,3-butadiene and its major metabolites in somatic and germ cells of mice, rats and man" is presented. Results of the project are summarized on the detection of DNA and hemoglobin adducts, on the cytotoxic and clastogenic effects in somatic and germinal cells of mice and rats, on the induction of somatic mutations at the hprt locus of experimental rodents and occupationally exposed workers, on the induction of dominant lethal mutations in mice and rats, and on heritable translocations induced in mice, after exposure to butadiene (BD) or its major metabolites, butadiene monoepoxide (BMO), diepoxybutane (DEB) and butadiene diolepoxide (BDE). The primary goal of this project was to collect experimental data on the genetic effects of BD in order to estimate the germ cell genetic risk to humans of exposure to BD. To achieve this, the butadiene exposure are based on data for heritable translocations and bone marrow micronuclei induced in mice and chromosome aberrations observed in lymphocytes of exposed workers. A doubling dose for heritable translocations in human germ cells of 4900 ppm/h is estimated, which, assuming cumulative BD exposure over the sensitive period of spermatogenesis, corresponds to 5-6 weeks of continuous exposure at the workplace to 20-25 ppm. Alternatively, the rate of heritable translocation induction per ppm/h of BD exposure is estimated to be approximately 0.8 per million live born, compared to a spontaneous incidence of balanced translocations in humans of approximately 800 per million live born. These estimates have large confidence intervals and are only intended to indicate orders of magnitude of human genetic risk. These risk estimates are based on data from germ cells of BD-exposed male mice. The demonstration that clastogenic damage was induced by DEB in preovulatory oocytes at doses which were not ovotoxic implies that additional studies on the response of mammalian female germ cells to BD and its metabolites are needed. The basic assumption of the above genetic risk estimates is that experimental mouse data obtained after BD exposure can be extrapolated to humans. Several points exist in the present report and in the literature which contradict this assumption: (1) the level of BMO-hemoglobin adducts was significantly elevated in BD-exposed workers; however, it was considerably lower than would have been predicted from comparable rat and mouse exposures; (2) the concentrations of the metabolites DEB and BMO were significantly higher in mouse than in rat blood after BD exposure. Thus, while metabolism of BD is qualitatively similar in the two species, it is quantitatively different; (3) no increase of HPRT mutations was shown in 19 workers exposed on average to 1.8 ppm of BD, while in a different population of workers from a US plant exposed on average to 3.5 ppm of BD, a significant increase of HPRT variants was detected; and (4) data from cancer bioassays and cancer epidemiology suggest that rat is a more appropriate model than mouse for human cancer risk from BD exposure. However, the dominant lethal study in rats gave a negative result. At present, we do not know which BD metabolite(s) may be responsible for the genetic effects even though the bifunctional alkylating agent DEB is the most likely candidate for the induction of clastogenic events. Unfortunately, methods to measure DEB adducts in hemoglobin or DNA are only presently being developed. Despite these several uncertainties the use of the mouse genetic data is regarded as a justifiable and conservative approach to human genetic risk estimation given the considerable heterogeneity observed in the biotransformation of BD in humans.