ABSTRACT The experimental results on chromosomal aberrations and spindle disturbances in mammalia... more ABSTRACT The experimental results on chromosomal aberrations and spindle disturbances in mammalian liver cells for eight regioisomers of pyrene, benzo(a)pyrene and phenanthrene quinones were compared with the AM1 calculated stereoelectronic descriptors. The electronic structure of the parent compounds as well as the corresponding radical anions, were evaluated. Two groups of reactivity descriptors were specified evaluating the mechanisms of genotoxicity of quinones that were recently proposed by us. The first group of parameters (e.g., electronic gap) describes potency of chemicals as cross-linkers of cellular macromolecules, whereas the second group (e.g., electronegativity, frontier orbital energies, their displacement and energy equivalence when going from quinones to the respective intermediate anion-radicals) assesses the one electron reduction efficiency. The ordering of quinones, according to their theoretically estimated reactivities, was found to be consistent with the experimental genotoxicity data. It was concluded that genotoxic activity of studied quinones is an integrated effect of two mechanisms. The prevailing one of these mechanisms affects the qualitative difference in the genotoxic effect of quinones. The benzo(a)pyrene and pyrene quinones were predicted to be more active cross-link inducers and more effective oxidants than phenanthrene quinones.
Scandinavian Journal of Work, Environment & Health
The possible genetic effects produced by styrene have been investigated by means of different met... more The possible genetic effects produced by styrene have been investigated by means of different methodologies in several biological organisms: (a) the induction of point mutation has been investigated in Salmonella typhimurium (reverse mutation), in the yeast Schizosaccharomyces pombe (forward mutation), both in vitro and in vivo, in the host-mediated assay of mice, and in the Chinese hamster cell line grown in vitro (V-79) (forward mutation); (b) the induction of chromosome mutation has been investigated in vivo, in mice, through the analysis of the presence of chromosome aberrations in bone marrow cells of treated animals; (c) the production of DNA (deoxyribonucleic acid) damage and the stimulation of DNA repair synthesis have been evaluated from measurements of unscheduled DNA synthesis in a heteroploid human cell line (EUE) and gene-conversion produced in the yeast Saccharomyces cerevisiae treated in vitro and in vivo (host-mediated assay). All the in vitro studies have been developed by the testing of the styrene in the presence of a metabolic activating system obtained with a mouse liver microsomal preparation. Styrene oxide, one of the in vivo metabolites of styrene with electrophilic properties towards DNA molecules, have also been tested in similar systems. Styrene was not mutagenic in all the systems tested; styrene oxide, on the contrary, was shown to be an active mutagen, independently of the genetic system under evaluation.
Scandinavian journal of work, environment & health, 1978
The possible genetic effects produced by styrene have been investigated by means of different met... more The possible genetic effects produced by styrene have been investigated by means of different methodologies in several biological organisms: (a) the induction of point mutation has been investigated in Salmonella typhimurium (reverse mutation), in the yeast Schizosaccharomyces pombe (forward mutation), both in vitro and in vivo, in the host-mediated assay of mice, and in the Chinese hamster cell line grown in vitro (V-79) (forward mutation); (b) the induction of chromosome mutation has been investigated in vivo, in mice, through the analysis of the presence of chromosome aberrations in bone marrow cells of treated animals; (c) the production of DNA (deoxyribonucleic acid) damage and the stimulation of DNA repair synthesis have been evaluated from measurements of unscheduled DNA synthesis in a heteroploid human cell line (EUE) and gene-conversion produced in the yeast Saccharomyces cerevisiae treated in vitro and in vivo (host-mediated assay). All the in vitro studies have been devel...
Epichlorohydrin (ECH), a direct mutagen in vitro, did not induce chromosomal aberrations in bone-... more Epichlorohydrin (ECH), a direct mutagen in vitro, did not induce chromosomal aberrations in bone-marrow cells of CD1 mice given single oral doses of 50 and 200 mg/kg in water. The ECH diol derivative (3-chloro-1,2-propanediol) was tested in vitro by a forward-mutation assay on the yeast Schizosaccharomyces pombe and showed a weak but significant mutagenic effect. The failure of ECH to induce mutagenic effects appears to be due to the rapid metabolic clearance of the compound in vivo. ECH blood kinetics at both doses, and at the same time the concentration of the diol, were determined. ECH rapidly disappeared from mouse blood, being no longer detectable 20 min after treatment. In contrast, 3-chloro-1,2-propanediol was measurable up to 5 h after dosage. No difference was observed in the kinetic and metabolic behavior of ECH after single and repeated doses (50 and 200 mg/kg/day for 7 days). When 3-chloro-1,2-propanediol was tested, neither glutathione depletion nor epoxide hydrolase inhibition (evaluated with both styrene-7,8-oxide and ECH as substrates) could be detected in mouse liver. Finally, no difference in ECH blood kinetics or metabolism were observed in experiments in which the compound was administered (200 mg/kg) intraperitoneally in water or orally as a solution in dimethyl sulfoxide.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 1997
Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lympho... more Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lymphocytes of human populations have been reported by various authors. Personal characteristics seem to account for a significant proportion of this variability. Several studies investigating the role of age as a confounding factor in cytogenetic biomonitoring found an age-related increase of micronucleus (MN) frequency, whereas contradictory results were reported for chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). We have quantitatively evaluated the effect of age on SCE, CA, and MN through the analysis of a population sample that included data from several biomonitoring studies performed over the last few decades in 12 Italian laboratories. The large size of the data set, i.e., more than 2000 tests for each end point, allowed us to estimate the independent effect of age, taking into account other covariates, such as sex, smoking habits, occupational exposure, and inter-...
Mutation Research/Environmental Mutagenesis and Related Subjects, 1996
Baseline frequencies of chromosome aberrations (CAs) were assessed in three samples of healthy in... more Baseline frequencies of chromosome aberrations (CAs) were assessed in three samples of healthy individuals, 60 living in a rural area (Po Delta), 134 in Pisa downtown and 116 in Cascina, a small town near Pisa, Italy. The three groups were similar for average age, sex ratio, smoking, drinking habit, and occupation. Multifactor ANOVA showed that CA frequencies increased significantly with age (p < 0.0001 excluding and including gaps), and with smoking habit (p = 0.0045 including gaps; p = 0.04 excluding gaps). Gender, drinking habit and occupation exerted no statistically significant effects. Multifactor ANOVA showed also a significant effect of the site of residence on the frequency of the CA, including gaps (p = 0.0003) and excluding gaps (p = 0.03). The CA frequency of the Pisa samples was statistically significantly higher than that of the Po Delta samples. Air pollution was considered to be a possible factor in determining the observed differences among the sites of residence, as levels of air pollutants (SO2 and TSP, total suspended articles) were more elevated in Pisa and Cascina than in the Po Delta. In addition, respiratory symptoms used as indirect indicators of air pollution at individual level were significantly more frequent in the Pisa population than in Cascina or in the Po Delta. These findings might support the hypothesis that air-pollution levels, even within E.E.C. (European Economic Community) air-quality standards, may influence baseline CA frequencies.
ABSTRACT The experimental results on chromosomal aberrations and spindle disturbances in mammalia... more ABSTRACT The experimental results on chromosomal aberrations and spindle disturbances in mammalian liver cells for eight regioisomers of pyrene, benzo(a)pyrene and phenanthrene quinones were compared with the AM1 calculated stereoelectronic descriptors. The electronic structure of the parent compounds as well as the corresponding radical anions, were evaluated. Two groups of reactivity descriptors were specified evaluating the mechanisms of genotoxicity of quinones that were recently proposed by us. The first group of parameters (e.g., electronic gap) describes potency of chemicals as cross-linkers of cellular macromolecules, whereas the second group (e.g., electronegativity, frontier orbital energies, their displacement and energy equivalence when going from quinones to the respective intermediate anion-radicals) assesses the one electron reduction efficiency. The ordering of quinones, according to their theoretically estimated reactivities, was found to be consistent with the experimental genotoxicity data. It was concluded that genotoxic activity of studied quinones is an integrated effect of two mechanisms. The prevailing one of these mechanisms affects the qualitative difference in the genotoxic effect of quinones. The benzo(a)pyrene and pyrene quinones were predicted to be more active cross-link inducers and more effective oxidants than phenanthrene quinones.
Scandinavian Journal of Work, Environment & Health
The possible genetic effects produced by styrene have been investigated by means of different met... more The possible genetic effects produced by styrene have been investigated by means of different methodologies in several biological organisms: (a) the induction of point mutation has been investigated in Salmonella typhimurium (reverse mutation), in the yeast Schizosaccharomyces pombe (forward mutation), both in vitro and in vivo, in the host-mediated assay of mice, and in the Chinese hamster cell line grown in vitro (V-79) (forward mutation); (b) the induction of chromosome mutation has been investigated in vivo, in mice, through the analysis of the presence of chromosome aberrations in bone marrow cells of treated animals; (c) the production of DNA (deoxyribonucleic acid) damage and the stimulation of DNA repair synthesis have been evaluated from measurements of unscheduled DNA synthesis in a heteroploid human cell line (EUE) and gene-conversion produced in the yeast Saccharomyces cerevisiae treated in vitro and in vivo (host-mediated assay). All the in vitro studies have been developed by the testing of the styrene in the presence of a metabolic activating system obtained with a mouse liver microsomal preparation. Styrene oxide, one of the in vivo metabolites of styrene with electrophilic properties towards DNA molecules, have also been tested in similar systems. Styrene was not mutagenic in all the systems tested; styrene oxide, on the contrary, was shown to be an active mutagen, independently of the genetic system under evaluation.
Scandinavian journal of work, environment & health, 1978
The possible genetic effects produced by styrene have been investigated by means of different met... more The possible genetic effects produced by styrene have been investigated by means of different methodologies in several biological organisms: (a) the induction of point mutation has been investigated in Salmonella typhimurium (reverse mutation), in the yeast Schizosaccharomyces pombe (forward mutation), both in vitro and in vivo, in the host-mediated assay of mice, and in the Chinese hamster cell line grown in vitro (V-79) (forward mutation); (b) the induction of chromosome mutation has been investigated in vivo, in mice, through the analysis of the presence of chromosome aberrations in bone marrow cells of treated animals; (c) the production of DNA (deoxyribonucleic acid) damage and the stimulation of DNA repair synthesis have been evaluated from measurements of unscheduled DNA synthesis in a heteroploid human cell line (EUE) and gene-conversion produced in the yeast Saccharomyces cerevisiae treated in vitro and in vivo (host-mediated assay). All the in vitro studies have been devel...
Epichlorohydrin (ECH), a direct mutagen in vitro, did not induce chromosomal aberrations in bone-... more Epichlorohydrin (ECH), a direct mutagen in vitro, did not induce chromosomal aberrations in bone-marrow cells of CD1 mice given single oral doses of 50 and 200 mg/kg in water. The ECH diol derivative (3-chloro-1,2-propanediol) was tested in vitro by a forward-mutation assay on the yeast Schizosaccharomyces pombe and showed a weak but significant mutagenic effect. The failure of ECH to induce mutagenic effects appears to be due to the rapid metabolic clearance of the compound in vivo. ECH blood kinetics at both doses, and at the same time the concentration of the diol, were determined. ECH rapidly disappeared from mouse blood, being no longer detectable 20 min after treatment. In contrast, 3-chloro-1,2-propanediol was measurable up to 5 h after dosage. No difference was observed in the kinetic and metabolic behavior of ECH after single and repeated doses (50 and 200 mg/kg/day for 7 days). When 3-chloro-1,2-propanediol was tested, neither glutathione depletion nor epoxide hydrolase inhibition (evaluated with both styrene-7,8-oxide and ECH as substrates) could be detected in mouse liver. Finally, no difference in ECH blood kinetics or metabolism were observed in experiments in which the compound was administered (200 mg/kg) intraperitoneally in water or orally as a solution in dimethyl sulfoxide.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 1997
Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lympho... more Intra- and interindividual variations of baseline frequencies of cytogenetic end points in lymphocytes of human populations have been reported by various authors. Personal characteristics seem to account for a significant proportion of this variability. Several studies investigating the role of age as a confounding factor in cytogenetic biomonitoring found an age-related increase of micronucleus (MN) frequency, whereas contradictory results were reported for chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs). We have quantitatively evaluated the effect of age on SCE, CA, and MN through the analysis of a population sample that included data from several biomonitoring studies performed over the last few decades in 12 Italian laboratories. The large size of the data set, i.e., more than 2000 tests for each end point, allowed us to estimate the independent effect of age, taking into account other covariates, such as sex, smoking habits, occupational exposure, and inter-...
Mutation Research/Environmental Mutagenesis and Related Subjects, 1996
Baseline frequencies of chromosome aberrations (CAs) were assessed in three samples of healthy in... more Baseline frequencies of chromosome aberrations (CAs) were assessed in three samples of healthy individuals, 60 living in a rural area (Po Delta), 134 in Pisa downtown and 116 in Cascina, a small town near Pisa, Italy. The three groups were similar for average age, sex ratio, smoking, drinking habit, and occupation. Multifactor ANOVA showed that CA frequencies increased significantly with age (p < 0.0001 excluding and including gaps), and with smoking habit (p = 0.0045 including gaps; p = 0.04 excluding gaps). Gender, drinking habit and occupation exerted no statistically significant effects. Multifactor ANOVA showed also a significant effect of the site of residence on the frequency of the CA, including gaps (p = 0.0003) and excluding gaps (p = 0.03). The CA frequency of the Pisa samples was statistically significantly higher than that of the Po Delta samples. Air pollution was considered to be a possible factor in determining the observed differences among the sites of residence, as levels of air pollutants (SO2 and TSP, total suspended articles) were more elevated in Pisa and Cascina than in the Po Delta. In addition, respiratory symptoms used as indirect indicators of air pollution at individual level were significantly more frequent in the Pisa population than in Cascina or in the Po Delta. These findings might support the hypothesis that air-pollution levels, even within E.E.C. (European Economic Community) air-quality standards, may influence baseline CA frequencies.
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