PubMed Health⌕ Search

Biomedical subjects

P Mozzoni

Publications and source records attributed to P Mozzoni.

12 recordsLinked to original sources
PubMed2003

Glutathione S-transferases M1-1 and T1-1 as risk modifiers for renal cell cancer associated with occupational exposure to chemicals.

AIMS: To investigate the possible interaction between occupational risk factors and genotype for glutathione S-transferases M1 and T1 (GSTM1 and GSTT1) in renal cell cancer (RCC). METHODS: One hundred patients with RCC and 200 outpatient controls were enrolled at Parma University Hospital. The polymorphisms of glutathione S-transferase M1-1 (GSTM1) and T1-1 (GSTT1) were investigated by PCR; occupational history was collected by a structured questionnaire. RESULTS: Subjects with GSTM1 present genotype showed higher risks for RCC, compared to GSTM1 null subjects, if exposed to metals (OR 2.73; 95% CI 0.91 to 8.22 v 1.14; 95% CI 0.46 to 2.82) or pesticides (OR 3.46; 95% CI 1.12 to 10.74 v 1.59; 95% CI 0.48 to 5.34). The GSTT1 present genotype also enhanced the risk (about twofold) of RCC among subjects exposed to solvents and pesticides, compared with those GSTT1 null. CONCLUSIONS: Results support the hypothesis that GSTM1 and GSTT1 polymorphisms can interact with several occupational exposures to significantly modify the risk of RCC among exposed subjects.

Aged↗
PubMed2001

Polymorphism of xenobiotic-metabolizing enzymes and excretion of styrene-specific mercapturic acids.

The role of polymorphic xenobiotic-metabolizing enzymes in the interindividual variability of phenylhydroxyethyl mercapturic acids (PHEMAs) was investigated in 56 styrene-exposed workers. Ambient monitoring was carried out using passive personal samplers (geometric mean, 157 mg/m3 8-h time-weighted average; geometric standard deviation, 2.90). Biomonitoring was based on mandelic acid and phenylglyoxylic acid in urine spot samples collected at the end of the work shift ("end-of-shift") and prior to the subsequent shift ("next morning"). Four PHEMA diastereoisomers, namely (R,R)-M1, (S,R)-M1, (S,R)-M2, and (R,R)-M2, were determined by HPLC/tandem mass spectrometry. The genotypes of glutathione S-transferases M1-1 (GSTM1), T1-1 (GSTT1) and P1-1 (GSTP1), and microsomal epoxide hydrolase (EPHX) were characterized by PCR-based methods. Workers bearing the GSTM1pos genotype showed PHEMA concentrations five and six times higher (in end-of-shift and next-morning samples, respectively) as compared to GSTM1null people. In GSTM1pos subjects, (R,R)-M1 was the main mercapturate affected by the GSTM1 status, accounting for 54 and 68% of total PHEMAs in end-of-shift and next-morning samples, respectively. Compared to GSTM1null, GSTM1pos subjects excreted more -M1 than -M2 and more (R,R)-M1 and (S,R)-M2 than (S,R)-M1 and (R,R)-M2 diastereoisomers. Thus, GSTM1-1 is the main isoenzyme catalyzing GSH-conjugation of styrene-7,8-oxide in humans and it seems to act in a regio- and stereoselective way. PHEMAs cannot be recommended as biomarkers of exposure to styrene, unless the GSTM1 genotype is considered in data interpretation. Their role as biomarkers of susceptibility deserves further studies.

Acetylcysteine↗
PubMed2001

Polymorphism of quinone-metabolizing enzymes and susceptibility to ozone-induced acute effects.

The role of the genetic polymorphism of NAD(P)H:quinone oxidoreductase (NQO1) and glutathione-S-transferase micro-1 (GSTM1) in the responsiveness to O(3)-induced acute effects was investigated in 24 healthy nonsmokers performing 2-h bike rides at ambient O(3) varying from 32 to 103 ppb. Before and after rides, each subject performed spirometric tests and provided a blood sample for the measurement of the Clara cell protein CC16. NQO1 and GSTM1 polymorphisms were characterized by polymerase chain reaction- based methods. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct was also measured in DNA of peripheral leukocytes. Rides at O(3) > 80 ppb resulted in significant decrements of pulmonary function tests and increased levels of serum CC16, consistent with mild impairment in respiratory function and increased lung epithelial permeability, respectively. Whereas NQO1wt and GSTM1null subjects showed both functional changes and increased serum CC16 after acute O(3) exposure, people with other haplotypes showed a rise in serum CC16 but no changes in lung function tests. In NQO1wt and GSTM1null subjects, partial correlation analysis showed that functional decrements and increased serum CC16 are closely associated with each other and with O(3) levels, whereas no such relationships were found among subjects bearing other haplotypes. An increased reaction rate between O(3) and hydroquinones would be consistent with the greater increase in 8-OHdG after O(3) exposure in this "susceptible" group.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1999

Biomarkers of dose and susceptibility in cyclists exposed to monoaromatic hydrocarbons.

A quasi-experimental field study was carried out in 24 volunteers with the aim of: (i) assessing personal exposure to aromatic hydrocarbons polluting urban areas; and (ii) exploring the role of polymorphic enzymes relevant to the biotransformation of benzene in the inter-individual variability of biomarkers. Each subject covered by bicycle: (i) inner city routes with often jammed traffic; and (ii) open rural routes. Time-weighted average airborne concentrations of benzene, toluene, ethylbenzene and xylenes (BTEX) were determined during 2-h runs. BTEX were determined by solid-phase micro-extraction (SPME) followed by gas chromatography coupled with mass spectrometry (GC-MS) in blood and spot urine samples collected just before and immediately after the runs. Urinary t,t-muconic acid was measured by high performance liquid chromatography (HPLC)-UV. Genotypes of epoxide hydrolase (EH) and glutathione-S-transferase class mu-1 (GSTM1) were also characterised. As compared to pre-run values, benzene and toluene in blood, and toluene and xylenes in urine significantly increased after urban runs. Urinary t,t-muconic acid was significantly higher in post-run samples after both urban (P < 0.001) and rural runs (P < 0.05). Despite a narrow range of exposure levels, a significant relationship was observed between airborne benzene and post-run t,t-muconic acid (r2 = 0.349, P < 0.00). When subgroups were distinguished according to EH and GSTM, subjects bearing both the EH wild type and GSTM 'null' genotype showed significant exposure-related changes in t,t-muconic acid excretion. Even at very low exposure levels, a 2-h bike run in a polluted urban environment may give rise to measurable changes in biomarkers of internal dose of selected aromatic hydrocarbons. Genetically-based metabolic differences may account for part of the inter-individual variability of biomarkers of exposure.

Adult↗
PubMed1997

Therapeutic potential of antiidiotypic single chain antibodies with yeast killer toxin activity.

Single chain fragment (ScFv) antiidiotypic antibodies (antilds) of a killer toxin (KT) from the yeast Pichia anomala have been produced by recombinant DNA methodology from the splenic lymphocytes of mice immunized by idiotypic vaccination with a KT-neutralizing monoclonal antibody (Mab KT4). ScFv KT-like antilds (KTIdAb) react with specific Candida albicans KT cell wall receptors (KTR) exerting a candidacidal activity in vitro could be neutralized by adsorption with Mab KT4. ScFv KTIdAb displayed an effective therapeutic activity in an experimental model of rat candidal vaginitis.

Animals↗
PubMed1996

Killer factor interference in mixed opportunistic yeast cultures.

The interaction of the killer yeast Pichia anomala UP 25F with the killer toxin-sensitive clinical isolate Candida albicans UCSC 10S and its natural toxin-resistant mutant derivative C. albicans UCSC 10R were studied under various conditions. A differential inhibition was shown to occur in vitro at pH and temperature values, which are not encountered in vivo, only by using preformed killer toxin, since antagonism due to yeast growth proved to be predominant on the killer effect. Under adverse growth conditions, the P. anomala killer yeast proved to be able to produce an anatoxin antigenically related to the active or heat inactivated killer toxin. These findings suggest that killer toxins may not function as potential virulence factors in the competition between the opportunistic killer yeast P. anomala and sensitive microorganisms for colonization in the course of natural human infections.

Antibiosis↗
PubMedDate not supplied

Exposure to hydrocarbons and renal disease: an experimental animal model.

The association between hydrocarbon exposure and chronic glomerulonephritis is still a controversial scientific issue. Recent epidemiological evidence suggests a role of exposure to hydrocarbons in the progression of glomerulonephritis towards chronic renal failure. The present experimental study on rats has been designed to assess the possible role of styrene in the progression of adriamycin (ADR) nephrosis, a well known model of renal fibrosis following nephrotic syndrome induced by ADR. Female Sprague-Dawley rats were exposed to styrene, 300 ppm, 6 h/day, 5 days/week for 12 weeks (group 1); treated with ADR, 2 mg/Kg, i.v., twice on day 1 and day 15 of the study (group 2); Additional groups of animals received both the styrene and ADR treatments (group 3) or served as controls (group 4). The urinary excretion of total and single proteins (albumin, Retinol-Binding Protein (RBP), Clara Cell 16 Kd protein (CC16), fibronectin) was measured monthly, whereas histopathology and determinations requiring blood sampling were carried out at the end of the experiment. A progressive increase in total proteinuria, falling in the nephrotic range already by the 6th week was observed in ADR-treated groups. Styrene exposure caused up to a 3- to 5-fold increase as compared to controls. Co-exposure to ADR and styrene also resulted in a proteinuria much greater than that caused by ADR alone. The interactive effect of styrene and ADR was statistically significant for albuminuria and urinary fibronectin. A similar response was observed for glomerular filtration rate at the end of the experiment, styrene-exposed animals showing hyperfiltration as compared to their respective control group. At the end of the experiment, histopathological scoring for interstitial infiltration and fibrosis was also significantly higher in styrene-treated animals as compared to their respective control groups. In ADR-treated rats, low molecular weight proteinuria (l.m.w.p.) was only slightly affected, suggesting minimal tubular dysfunction associated with extensive tubular atrophy. However, styrene-exposed animals showed l.m.w.p. higher than their respective controls. In summary, in this animal model we were able to confirm both styrene-induced microproteinuria, mainly albuminuria and minor increases in l.m.w.p., observed among occupationally exposed workers and the role of hydrocarbon exposure as a factor accelerating the progression of renal disease suggested by epidemiological investigations in patients suffering from chronic renal disease. Whereas in rats exposed to styrene only, microproteinuria was stable over time and minor histopathological changes were noted at the end of the experiment, evidence of a role of solvent exposure in the progression of ADR nephropathy was obtained in terms of both renal dysfunction and interstitial fibrosis. The mechanistic basis of styrene-ADR interaction is unclear. However, experimental evidence is consistent with epidemiological findings suggesting the need to avoid solvent exposure in patients suffering from renal diseases.

Albuminuria↗
PubMedDate not supplied

[Renal effects of low doses of mercury].

OBJECTIVES: The present study was aimed at investigating early markers of renal damage and dysfunction in subjects exposed to low doses of mercury from different sources. Different groups of subjects were examined with urinary Hg excretion (HgU) ranging from 0.1 to 35.0 micrograms/g creatinine: 122 occupationally exposed workers, 22 subjects living in a non-polluted area, but consuming large amounts of tuna and sword fish, and 197 controls. METHODS: Several markers of renal changes were measured in urine (albumin, fibronectin, beta 2-microglobulin, retinol-binding protein, tubular antigens, N-acetyl-beta-D-glucosaminidase activity) and serum (beta 2-microglobulin and cystatin C). Serum autoantibodies towards collagen, laminin and tubular antigens were assessed in subjects with abnormal renal markers. The role of glutathione-S-tranferases GSTT1 and GSTM1 polymorphisms in the inter-individual variability of biological response to Hg was also investigated. RESULTS: Renal markers were not correlated with HgU. None of such markers differed significantly between exposed workers and controls, except for urinary beta 2-microglobulin, which was decreased in Hg-exposed workers (GM = 55.8 vs 86.6 micrograms/g creatinine), in the absence of any changes in serum concentration. Subjects usually eating tuna and sword fish showed an increased urinary excretion of beta 2-microglobulin, albumin and fibronectin. Serum titres of auto-antibodies did not differ between the groups. Neither in controls nor in exposed workers were the observed differences modified by the GSTM1 and GSTT1 genotypes. CONCLUSION: The present study did not provide evidence of any changes in kidney integrity and function in subjects exposed to very low levels of inorganic Hg resulting in urinary Hg lower than 35 micrograms/g creatinine. Nor did we obtain evidence of Hg-induced autoimmunity towards kidney components. The potential modifying role of GST polymorphisms could not be clarified in the absence of effects associated with exposure to the risk factor, i.e., to inorganic Hg. Preliminary data suggesting nephrotoxic effects of organic Hg from a diet rich in large fish resulting in increased levels of both blood and urinary Hg--which however did not exceed 20 micrograms/g creatinine--deserves further investigation.

Adult↗
PubMedDate not supplied

[Genetic polymorphism of biotransforming enzymes and genotoxic effects of styrenes].

A cross-sectional study was carried out on laminators producing glass-fibre reinforced plastics, to evaluate the role of genetic polymorphism of xenobiotic metabolising enzymes on the genotoxicity of styrene. Clastogenic effects, evaluated by the micronucleus test, are related with end-of-shift urinary concentration of 4-vinylphenol and seem to be modulated by NQO1 polymorphism; aneuploidogenic effects, evaluated by the identification of centromers in micronuclei using the fluorescence in situ hybridisation technique with a pancentromeric probe, are related with before-shift urinary levels of mandelic and phenylglyoxylic acids and seem to be modulated by the GSTM1 polymorphism.

Adult↗
PubMedDate not supplied

[ALAD polymorphism and indicators of dose and effects of occupational exposure to inorganic lead].

The delta-aminolevulinate dehydrase (ALAD) genetic polymorphism was investigated along with biomarkers of lead exposure and effect on 333 male workers, occupationally exposed to lead, with blood lead levels (PbB) higher than 100 microg/l. ALAD genotype frequencies were distributed as expected among Caucasians. Workers bearing at least one ALAD-2 allele showed PbB values slightly higher than those from ALAD-1-1 subjects, who also exhibited higher urinary delta-aminolevulinic acid (ALAU) and blood zinc protoporphyrin (ZPP) levels. The plasmatic lead (PbP)/PbB ratio was similar in both groups. Exposure and effect biomarkers were significantly each other correlated among ALAD-1-1 subjects only, who showed also a significant inverse relationship between ALAD activity and ZPP values. Results confirm previous studies, supporting the hypothesis that ALAD polymorphism may interfere with toxico-kinetic and toxico-dynamic parameters of occupational exposure to Pb.

Adult↗
PubMedDate not supplied

[Heme oxygenase 1 expression in foundry workers].

Heme oxygenase 1 (HO-1) catalyses the oxidation of heme to biliverdin, and its expression is induced by oxidative stress. This study was aimed at assessing the role of metabolic polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1, EPHX) in the modulation of HO-1 gene expression in 37 foundry workers. Blood and urine samples were obtained at the beginning (BS) and at the end (ES) of work shift, in February (T1) and June (T2). Urinary 1-hydroxypyrene (1-OHP) was measured as a tracer of PAH exposure. HO-1 gene expression in ES samples normalized to BS values (HO-1 ES/BS) was higher at T2 respect to T1. HO-1 gene induction was related to ES 1-OHP when considering either T2 samples or the combination of the two samplings. HO-1 ES/BS was significantly increased in subjects with at least a mutant allele for GSTP1 as compared to subjects with GSTP1AA genotype (1.23 +/- 0.002 vs 0.88 +/- 0.002, p < 0.05). Only in subjects with at least one vari.nt allele for GSTP1, a positive correlation between HO-1 ET/IT expression and 1-OHP FT levels was observed (r2 = 0.21, p = 0.016). The present study demonstrates a correlation between PAH exposure, as assessed by urinary 1-OHP, and the induction of HO-1 expression. Such a correlation seems to be limited to subjects bearing variant alleles for GSTP1. At the same exposure levels, these subjects showed a greater expression of HO-1 FT as compared to subjects with GSTP1 wild type genotype, possibly due to a higher oxidative stress in the subjects expressing the mutant GSTP1-1 isoform, which could imply a limited scavenging capacity.

Adult↗