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R Lucchini

Publications and source records attributed to R Lucchini.

At least 19 recordsLinked to original sources
PubMed2001

Nucleosome positioning at the replication fork.

In order to determine the time required for nucleosomes assembled on the daughter strands of replication forks to assume favoured positions with respect to DNA sequence, psoralen cross-linked replication intermediates purified from preparative two-dimensional agarose gels were analysed by exonuclease digestion or primer extension. Analysis of sites of psoralen intercalation revealed that nucleosomes in the yeast Saccharomyces cerevisiae rDNA intergenic spacer are positioned shortly after passage of the replication machinery. Therefore, both the 'old' randomly segregated nucleosomes as well as the 'new' assembled histone octamers rapidly position themselves (within seconds) on the newly replicated DNA strands, suggesting that the positioning of nucleosomes is an initial step in the chromatin maturation process.

Base Sequence↗
PubMed2000

Mechanism of neurobehavioral alteration.

Behavioral toxicology is an emerging field which is becoming increasingly important in risk assessment of exposure to neurotoxic substances, due to the high sensitivity of behavior towards neurotoxic action and the integration in behavioral functions of several underlying processes and neurofunctions, such as motor, sensory, attention, motivational. Whenever it is difficult to isolate the relative contribution of sensory, motor, arousal, or cognitive factors that contribute to an observed behavioral change, possible mechanism of behavioral alteration may rely on the involvement of neurotransmitters, such as the dopaminergic system and catecholamines metabolism. Examples are given of different behavioral types of changes induced in humans by organic solvents (styrene), metals (manganese) and anaesthetic gases, based on a possible common underlying mechanism of toxicity.

Aggression↗
PubMed2000

Are current biomarkers suitable for the assessment of manganese exposure in individual workers?

BACKGROUND: Whole blood and urinary manganese have been measured in occupational and environmental studies for the assessment of exposure. The aim of this study was to assess the relationship between the airborne concentrations of manganese and these biological indicators. METHODS: Environmental and biological monitoring was performed in a group of 94 employees in a ferroalloy production, who were exposed to manganese (Mn) oxides (MnO(2) and Mn(3)O(4)). The results were compared with those from a control group of 87 subjects not exposed to Mn. RESULTS: Mn exposure levels ranged between 5 and 740 micrograms/m(3), with arithmetic and geometric mean and median values being 202.6, 97.6, and 150 micrograms/m(3), respectively. Arithmetic and geometric means for Mn in total blood (MnB) were, respectively, 10.3+/-3.8 and 9.7 micrograms/L in the exposed and 5.9+/-1.7 and 5.7 micrograms/L in the controls. For urinary Mn (MnU), arithmetic and geometric means were, respectively, 4.9+/-3.6 and 3. 8 micrograms/L in the exposed and 1.2+/-1.4 and 0.7 micrograms/L in the controls. On a group comparison, a significant relationship was found between high and low exposed subgroups, identified according to Mn atmospheric concentrations (MnA), for both MnB (F value=38.0, P > 0.0001) and MnU (F value=36.1, P > 0.0001). On a linear relationship, a correlation was observed between MnA and MnB (r=0. 34; r(2)=0.112; P=0.001), whereas no association was found between MnA and MnU. A significant relationship emerged also between MnB and MnU (r=0.48, r(2)=0.23, P < 0.0001). No association was observed between an index of cumulative exposure and the biological indicators of exposure. CONCLUSIONS: These results confirm that MnB and MnU can discriminate groups of occupationally exposed workers from groups of nonexposed subjects. MnB is also related to the intensity of external exposure on a linear relationship, but given a high variability, it is not suitable for individual biological monitoring. Therefore, further research should focus on more accurate biomarkers of Mn exposure.

Biomarkers↗
PubMed2000

Replication of yeast rDNA initiates downstream of transcriptionally active genes.

In the yeast S. cerevisiae, ARS (autonomously replicating sequence) elements located in the intergenic spacers of the rRNA gene locus are infrequently activated as origins of replication. We analyzed the rARS activation with a combination of neutral/neutral (N/N) two-dimensional (2D) gel electrophoresis and either the intercalating drug psoralen, which in vivo specifically marks the transcribing gene copies, or the selective accessibility of restriction sites in transcriptionally active genes. We found that initiation of replication starts at those rARSs placed immediately downstream of transcribing rRNA genes. This correlation between transcription and replication is consistent with the presence of nucleosome-free enhancers at each transcriptionally active gene copy and suggests that the transcription factor Abf1p is involved in replication initiation at the ARS in the rDNA gene locus.

DNA Replication↗
PubMed2000

Brain magnetic resonance imaging and manganese exposure.

Due to its paramagnetic properties, manganese (Mn) can be effectively visualized by MRI. Mn accumulates selectively in the globus pallidus of basal ganglia, where it can produce high signals at brain magnetic resonance. These hyperintensities are bilateral, symmetrical, and visible in T1-weighted magnetic resonance imaging of different manganese overload conditions. A review of the literature shows identical findings in manganese exposed workers, hepatopatic patients, and patients undergoing total parenteral nutrition with excessive amount of manganese. Two indicators of exposure and hyperintensity were considered, represented respectively by the concentration of Mn in total blood (MnB), and the pallidal index (PI). These two indicators show a positive association, which indicates a possible continuum from normality to clinical stages both in workers occupationally exposed to Mn and in patients suffering from chronic liver disease. Since both MnB and PI show a high degree of variability, further research should be focused on the identification of more accurate indicators.

Brain↗
PubMed2000

Assessment of neurobehavioral performance as a function of current and cumulative occupational lead exposure.

A cross sectional field study was planned to assess neurotoxic effects caused by low-level occupational lead exposure. Two groups of 66 workers and 86 controls were examined with a battery including a questionnaire on neurotoxic symptoms, the measure of performance at neurobehavioral testing, the detection of visual contrast sensitivity, and the dosage of serum prolactin. Both current and cumulative exposure to lead were defined. The average PbB was 27.50 +/- 28 microg/dl (median 28, range 6-61) in the exposed and 8.11 +/- 4.47 microg/dl (median 7, range 2-21). The test results were controlled for possible confounders including age, schooling, alcohol and coffee intake. Significant differences were observed between exposed and controls regarding neurotoxic symptoms reporting, the exposed reporting more frequently mood changes and abnormal fatigue. The exposed subjects showed a decreased visual contrast sensitivity, and a marked increase of prolactin secretion. No changes emerged regarding neurobehavioral testing. The alterations observed resulted associated to the current lead exposure and not to the cumulative indices. A safe exposure level was calculated on the basis of dose-response relationship with prolactin alteration, yielding a PbB value of 10 microg/dl.

Adult↗
PubMed1997

Chromatin structure and methylation of rat rRNA genes studied by formaldehyde fixation and psoralen cross-linking.

By using formaldehyde cross-linking of histones to DNA and gel retardation assays we show that formaldehyde fixation, similar to previously established psoralen photocross-linking, discriminates between nucleosome- packed (inactive) and nucleosome-free (active) fractions of ribosomal RNA genes. By both cross-linking techniques we were able to purify fragments from agarose gels, corresponding to coding, enhancer and promoter sequences of rRNA genes, which were further investigated with respect to DNA methylation. This approach allows us to analyse independently and in detail methylation patterns of active and inactive rRNA gene copies by the combination of Hpa II and Msp I restriction enzymes. We found CpG methylation mainly present in enhancer and promoter regions of inactive rRNA gene copies. The methylation of one single Hpa II site, located in the promoter region, showed particularly strong correlation with the transcriptional activity.

Animals↗
PubMed1997

Motor function, olfactory threshold, and hematological indices in manganese-exposed ferroalloy workers.

A cross-sectional study was conducted in 35 male subjects randomly selected from workers of a ferroalloy production plant and exposed to manganese (Mn) oxides; the objective was to detect early signs of neurologic impairment. The subjects' mean age was 39.4 years (SD, 8. 4); the average exposure duration was 14.5 years (range, 5-29 years). A control group of industrial workers not exposed to neurotoxic chemicals and comparable in age and confounding factors was recruited. The intensity of Mn exposure was moderate, as reflected by airborne Mn concentrations in total dust averaging 193 [corrected] micro g/m3. Mn levels in blood (MnB) and urine (MnU) were significantly higher in the Mn-exposed workers than in control workers. A relationship (not found with MnU) was found between MnB and a cumulative exposure index calculated on the basis of air concentration and exposure history for each subject (r = 0.52; r2 = 0.27; P = 0.002). Psychomotor function scores were lower among Mn-exposed subjects. The Aiming score was negatively correlated with MnB in the exposed group. The olfactory threshold did not differ between the two groups, although it was negatively associated with MnU in the exposed group. The white blood cell count results were significantly higher in Mn-exposed subjects than in controls. These findings show that an increase in Mn body burden is associated with an impairment of motor functions, whereas the increased excretion of Mn is related to an increased olfactory perception. Changes in numbers of leukocytes could indicate possible interferences of Mn with the immunological system.

Air Pollutants, Occupational↗
PubMed1997

Prevention of Risks from Occupational Exposures to Antineoplastic Drugs: Consensus Document.

Ever-increasing numbers of cancer patients have been treated with antineoplastic drugs in the past few years. Among patients treated with these drugs, an increased risk of a "second neoplasm" has been observed, mainly as a function of increased life expectancy. On the basis of this observation, the International Agency for Research on Cancer has classified a number of antineoplastic drugs as carcinogenic or probably carcinogenic for humans. Various categories of workers are at risk for exposure to antineoplastic drugs, absorbing these substances mainly through inhalation or dermal contact. Although the absorbed doses are notably lower than those administered to patients, review of the literature reveals increased risks of spontaneous abortions and chromosomal aberrations in subjects who have worked without adequate protection. A working group, Prevention of Occupational Risks Due to Handling Antineoplastic Drugs in Health Care, was established by the Italian Institute of Prevention and Safety at Work (Istituto Superiore per la Prevenzione e Sicurezza sul Lavoro-ISPESL) in February 1995. This group reviewed the epidemiologic studies and research on cytogenetic indicators of genotoxicity in occupationally exposed subjects. In addition, the group made recommendations for environmental and biological monitoring of exposure and health surveillance, and developed guidelines for primary and secondary prevention. The group's recommendations are summarized in a consensus document, but cannot be considered definitive, since work practices continue to evolve and will have to be examined further in the future. Thus, more research is needed to achieve answers to the questions raised by the working group. The main topics to be addressed are indicated in the consensus document. In particular, it will be necessary to evaluate working conditions nationwide, using standardized protocols for risk assessment, to achieve precise estimates of workers' exposures.

Journal Article↗
PubMed1996

Proposal of a method for identifying exposure to hazardous chemicals in biomedical laboratories.

Controlling occupational exposure to chemical substances in biomedical laboratories is very complex because of the high number of compounds involved, and the rapid changes in analytical techniques and methods. On the other hand, evidence of increased mortality for malignant lymphoma and leukemia has been observed in laboratory technicians. This calls for more precise procedures of risk assessment to identify the specific substances that may be responsible for these effects. A model of hazard identification is presented, which includes the following steps: identification, classification and periodical updating of the chemical substances used in each analytical technique; evaluation of the variables that can influence the exposure; quantification of exposure using environmental measurements. The availability of such a procedure can be useful for the organization of health and epidemiological surveillance programs for the laboratory workers.

Clinical Laboratory Information Systems↗
PubMed1996

Neurotoxicity in operating room personnel working with gaseous and nongaseous anesthesia.

Occupational exposure to high concentrations of anesthetic gases (more than 500 ppm of nitrous oxide and more than 15 ppm of halothane and enflurane) can cause neurobehavioral effects in operating room personnel. Factors such as stress and work organization play an additional role in reducing performance capacities. It is still unclear whether these conditions may become the predominant factor in behavioral impairment when exposure to anesthetic gases is reduced; in addition, we wished to ascertain the extent of neurobehavioral and neuroendocrine effects at relatively low levels of exposure to such gases. Therefore the same group of 30 operating room personnel was examined with neurobehavioral tests during gaseous and nongaseous anesthesia. In this way, the neuropsychological performance was examined under the same stress conditions, but with different exposure levels to anesthetic gases. Serum cortisol was measured as an additional "biological stress indicator." Prolactin secretion was examined to study possible interference of anesthetic gases with the dopaminergic system. The results were compared with those in a control group of 20 hospital workers from other departments, with similar characteristics in respect of age, sex, and education. During work with gaseous anesthesia, average airborne concentrations (geometric mean) of nitrous oxide were 50.9 ppm (SD 20.8) on the first day of the working week, and 54.2 ppm (SD 22.1) on the last day of the working week, whereas average urinary nitrous oxide (geometric mean) were 21.54 micrograms/l on the first day of the working week and 25.67 micrograms/l on the last day of the working week. The operating room workers showed slower reaction times at the end of the week with gaseous anesthesia, compared with workers using nongaseous anesthesia and the control group. At the same time they also showed increased secretion of prolactin, whereas cortisol remained unchanged. Therefore, it can be concluded that lower levels of exposure to anesthetic gases (and not only high exposure levels) cause an impairment of neurobehavioral performance, with the action of stress being less relevant. The mechanism of anesthetics' neurotoxic action seems to be related to interference with the dopaminergic system.

Adult↗
PubMed1995

Replication of transcriptionally active chromatin.

In eukaryotic cells, active genes and their regulatory sequences are organized into open chromatin conformations in which nucleosomes can be modified, disrupted or totally absent. It has been proposed that these characteristic chromatin structures and their associated factors might be directly inherited by the newly synthesized daughter strands during chromosome duplication. Here we show that in the yeast Saccharomyces cerevisiae, replication machinery entering upstream of a transcriptionally active ribosomal RNA gene generates two newly replicated coding regions regularly packaged into nucleosomes, indicating that the active chromatin structure cannot be directly inherited at the replication fork. Whereas the establishment of an exposed chromatin conformation at some newly replicated rRNA gene promoters can occur shortly after the passage of the replication fork, regeneration of the active chromatin structure along the coding region is always a post-replicative process involving disruption of preformed nucleosomes.

Chromatin↗
PubMed1995

Immunological changes among workers occupationally exposed to styrene.

The functional status of the immune system was investigated in a group of 71 workers exposed to styrene and in 65 control subjects, recruited according to the same selection criteria and comparable as to sex, age, and confounding variables. Air and biological monitoring were used to characterize styrene exposure (median of the main urinary metabolites in the "next-morning" spot samples: 106 mg/g creatinine). Phenotypic analysis of peripheral blood lymphocytes (PBL) by automated flow cytometry revealed a reduced proportion of T lymphocyte subsets (CD3+, CD4+ and CD4+45+), with no changes in CD8+, and a higher proportion of B lymphocytes (CD19+) among styrene-exposed workers. The exposed workers showed a higher proportion of activation markers, namely DR and interleukin-2 receptors (CD25). Immunoglobulin subclasses were comparable in the two groups. An increased prevalence of abnormally low values was apparent for CD2+, CD3+, CD4+, CD4+45+ and CD11b subsets among workers exposed to styrene, whereas CD19+, DR+ and CD25+ showed an increased prevalence of abnormally high values. Natural killer-related phenotypes (CD56+, CD56+16+, and CD56+16-) were more expressed among styrene workers, with average increase of 30%. However, the frequency distribution of the lytic activity of natural killer cells against K-562 target cells was shifted towards lower values in the exposed workers as compared to control subjects. Dose-response relationships between indices of internal dose and prevalence of abnormal values were detectable for T lymphocyte subsets, NK phenotypes, and activation markers. These findings suggest that moderate exposure to styrene is associated with an altered distribution of lymphocyte subsets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Peripheral markers of catecholamine metabolism among workers occupationally exposed to manganese (Mn).

In a preliminary study of 11 men randomly selected in a ferro-alloy plant and of 15 control subjects, platelet monoamine oxidase (MAO) and serum dopamine beta-hydroxylase (DBH) activities were measured. A tendency towards lower MAO-B activity in the exposed workers as compared to control subjects (t = 1.95; P = 0.06) was found whereas DBH activity was similar. In the exposed group, a dose-effect relationship was noted between a manganese (Mn) cumulative exposure index (CEI) and DBH activity (R2 = 0.40, P < 0.05). Since DBH is an expression of catecholamine release, the relative increase in such activity could be envisaged as a compensatory mechanism to a reduced turnover rate as reflected by MAO-B activity. Owing to the limited sample size, these findings should be confirmed by further epidemiological and experimental studies.

Adult↗
PubMed1995

Transcription in the yeast rRNA gene locus: distribution of the active gene copies and chromatin structure of their flanking regulatory sequences.

In growing yeast cells, about half of the 150 tandemly repeated rRNA genes are transcriptionally active and devoid of nucleosomes. By using the intercalating drug psoralen as a tool to mark accessible sites along chromatin DNA in vivo, we found that the active rRNA gene copies are rather randomly distributed along the ribosomal rRNA gene locus. Moreover, results from the analysis of a single, tagged transcription unit in the tandem array are not consistent with the presence of a specific subset of active genes that is stably maintained throughout cell divisions. In the rRNA intergenic spacers of yeast cells, an enhancer is located at the 3' end of each transcription unit, 2 kb upstream of the next promoter. Analysis of the chromatin structure along the tandem array revealed a structural link between transcription units and adjacent, 3' flanking enhancer sequences: each transcriptionally active gene is flanked by a nonnucleosomal enhancer, whereas inactive, nucleosome-packed gene copies are followed by enhancers regularly packaged in nucleosomes. From the fact that nucleosome-free enhancers were also detected in an RNA polymerase I mutant strain, we interpret these open chromatin structures as being the result of specific protein-DNA interactions that can occur before the onset of transcription. In contrast, in this mutant strain, all of the rRNA coding sequences are packaged in nucleosomal arrays. This finding indicates that the establishment of the open chromatin conformation on the activated gene copies requires elongating RNA polymerase I molecules advancing through the template.

Cell Division↗
PubMed1995

Neurobehavioral effects of manganese in workers from a ferroalloy plant after temporary cessation of exposure.

OBJECTIVES: The goal of this study was to assess long-term neurobehavioral effects associated with low airborne concentrations of manganese in a ferroalloy plant. METHODS: During a period of forced cessation of work (1 to 42 d) neurobehavioral performance on tests of simple reaction time, finger tapping, digit span, additions, symbol digit, and shapes comparison was evaluated for 58 workers exposed from 1 to 28 (mean 13, SD 7) years to manganese. Airborne manganese concentrations in total dust had been reduced in the last 10 years from 70-159 micrograms x m-3 (geometric means in different areas) to 27-270 micrograms x m-3. For each worker, manganese concentrations in blood and urine were measured, and a cumulative exposure index was also calculated. RESULTS: Blood manganese and urinary manganese ranged from 4 to 18 micrograms x 1-1 (0.07 to 0.03 mumol x 1-1) and from 0.7 to 7 micrograms x 1-1 (0.01 to 0.13 mumol x 1-1) respectively. Significant relationships were found between the blood manganese and urinary manganese levels and between these biological measures and the cumulative exposure index. Correlations were also found between the blood manganese level, the urinary manganese level, and the cumulative exposure index and the following tests: finger tapping, symbol digit, digit span, and additions. The correlation coefficients increased as the latency time after the cessation of exposure and work seniority increased. CONCLUSIONS: The results support the hypothesis that the neurobehavioral effects observed at exposure levels well below current occupational standards are related to manganese body burden, which is better reflected by the blood manganese level after the cessation of exposure.

Adult↗
PubMed1994

Replication fork barriers in the Xenopus rDNA.

To investigate replication fork progression along the tandemly repeated rRNA genes of Xenopus laevis and Xenopus borealis, rDNA replication intermediates from dividing tissue culture cells were analyzed by two-dimensional gel electrophoresis. Analysis of the direction of replication in the rRNA coding regions revealed replication forks moving in both directions. However, in both frog species, polar replication fork barriers (RFB) arresting forks approaching the rRNA transcription units from downstream were identified. Whereas in X. borealis the RFB maps to a defined site close to the transcription terminator, in X. laevis the arrest of fork movement can occur at multiple positions throughout a 3' flanking repetitive spacer region. A short DNA element located near the respective RFB sites is shared between these two related frog species, suggesting its possible involvement in the arrest of replication fork movement. In a subset of rDNA repeats, these barriers cause an absolute block to replication fork progression, defining the sites where replicon fusion occurs, whereas in the remainder repeats, most probably in the non-transcribed gene copies, the replication machinery can pass the RFB sequences and replicate the rRNA transcription unit in a 3'-to-5' direction.

Animals↗