Patrizia Hrelia | Università di Bologna (original) (raw)
Papers by Patrizia Hrelia
Advances in Environmental Control Technology: Health and Toxicology, 1997
European Journal of Medicinal Chemistry, Dec 8, 2011
Mutation Research Genetic Toxicology and Environmental Mutagenesis, Jun 17, 2010
-Caryophyllene is a bi-cyclic sesquiterpene that occurs in essential oils from several plants. A... more -Caryophyllene is a bi-cyclic sesquiterpene that occurs in essential oils from several plants. A variety of biological activities have been ascribed to this compound. In particular, it seems to possess anticarcinogenic properties, due to its capability to induce detoxifying enzymes or to enhance, in vitro and in vivo, the natural killer cell-induced cytotoxicity against tumours. Conversely, the knowledge on the DNAdamaging activity of the substance and its modulation is scanty. Therefore, in this study, we aimed at evaluating the capability of -caryophyllene to protect cultured human lymphocytes from the genotoxic damage induced by ethyl methanesulfonate (EMS) and colcemid (COL) in the micronucleus assay. To investigate the mechanisms of action of this sesquiterpene, the cultures were treated with the compound before (pre-treatment), during (co-treatment) and after (post-treatment) treatment with the mutagens.
Teratogenesis Carcinogenesis and Mutagenesis, 1984
This study was designed to investigate the effect of ether anesthesia in rats, before i.p. inject... more This study was designed to investigate the effect of ether anesthesia in rats, before i.p. injections to induce the mono-oxygenase enzyme system, on biochemical properties of liver S9 fractions. Aminopyrine N-demethylase and p-nitroanisole O-demethylase activity levels, their stability, and lipid peroxidation were determined in S9 fractions after etherization (about 1 min in ether vapor chamber daily for 3 consecutive days, before i.p. injections of Na-phenobarbital and /3-naphthoflavone) and compared with controls receiving the same injections without etherization. The activities were slightly (but not significatively) enhanced after this treatment, but stability was markedly and significatively greater after 1 h of incubation in the conditions of the liver microsomal assay (+ 14.8% and +74.7 %, respectively); lipid peroxidation was strongly and significatively depressed (-76.0%). Etherization sufficient to kill the animals on the 4th day resulted in equally active but less stable S9 fraction enzymes. Dimethylnitrosamine (as a standard premutagen) was assayed with the D7 strain of Saccharomyces cerevisiae using S9 fractions obtained from both anesthetized and nonanesthetized rats. According to biochemical data, results obtained with S9 from partially anesthetized rats were comparable with the conventional ones (S9 from nonanesthetized rats). On the contrary, the use of more prolonged ether anesthesia, including one on the day the animals are killed, gives S9 fraction significantly less effective.
Drugs under experimental and clinical research
The genotoxicity of nitroimidazoles and, in particular, their potential carcinogenicity has been ... more The genotoxicity of nitroimidazoles and, in particular, their potential carcinogenicity has been demonstrated. In order to investigate the specific target organ(s) for these drugs or their metabolites, a method for measuring mutations in microorganisms, with reference to the metabolism of mammals, was used in mice. Metronidazole and azanidazole were tested for their ability to induce genetic effects in a diploid strain (D7) of Saccharomyces cerevisiae in the Intrasanguineous Host-Mediated Assay. The test compounds showed dose-related increases of point mutation and mitotic gene conversion frequencies in liver, kidney and lung. Azanidazole seemed to favour the kidney and the liver, although increases in genotoxicity were observed also in the lung. Metronidazole was toxic and induced both point mutation and mitotic gene conversion when recovered from the liver. Yeast recovered from the kidney and the lung showed an increase especially in point mutation. This work provides more information about the mechanisms involved in the mutagenicity of nitroimidazoles at the site of action.
Anticancer research
Background: Little is known regarding the potentially chemopreventive activity of cyanidin-3-O-‚g... more Background: Little is known regarding the potentially chemopreventive activity of cyanidin-3-O-‚glucopyranoside (Cy-g), the main anthocyanin present in the juice of pigmented oranges, apart from its antioxidant activity. After excluding a potential genotoxicity of Cy-g, its ability to induce apoptosis on transformed and normal T cells was analysed. In order to delineate the events leading to apoptosis, the expression of different proteins, known to be involved in apoptosis, was also measured. Materials and Methods: The evaluation of genotoxicity was performed by the micronucleus test. Flow cytometry was used for the analysis of apoptotic cells and proteins involved in the modulation of apoptosis. Results: Cy-g was nongenotoxic. Moreover, it induced apoptosis in both cell systems, modulated by an increase of p53 and bax proteins. Conclusion: These interesting biological properties should encourage further studies into the chemopreventive potential of Cy-g. Nevertheless, its activity in normal T cells underlines the need for extensive toxicological investigation.
PloS one, 2015
Socio-economic, cultural and environmental factors are becoming increasingly important determinan... more Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD). We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes) in a group of COPD patients. Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant'Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines. 229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage). Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis). Kaplan-Meier estimates showed a significant difference between survival...
Toxicological Sciences, 2015
DNA sequence and genetic factors alone cannot fully explain the many processes implicated in dise... more DNA sequence and genetic factors alone cannot fully explain the many processes implicated in diseases initiation and development. It is now well understood that additional factors are involved in a final resulting phenotype. Epigenetic modifications, heritable changes not affecting the DNA sequence, are a key phenomenon at the basis of normal growth and differentiation. However, these can be defective leading to diseases, such as cancer. An increasing body of literature reports the environmental and occupational exposure to a mixture of natural and man-produced substances leading to epigenetic alterations. The identification of key genetic and/or epigenetic events involved in chemical carcinogenesis is an important step towards the discovery of biomarkers that can be used to evaluate the exposure, predict biological effects, and prevent adverse health consequences. Here, we focus on epidemiological studies to review the most recent advances in understanding genetic and epigenetic factors in relation to particulate matter, benzene and polycyclic aromatic hydrocarbons exposure.
Acta Horticulturae, 2010
The fruit characteristics, level of some phenolic compounds (phenolic acids, flavonols) and antio... more The fruit characteristics, level of some phenolic compounds (phenolic acids, flavonols) and antioxidant capacity were determined in strawberries (Fragaria ananassa L., 'Favette') grown by conventional and biodynamic agricultural methods. In addition, the in vitro bioactivity of biodynamic and conventional strawberry extracts, in terms of antiproliferative activities in human colon carcinoma (Caco-2) cells, was also evaluated. The strawberry extracts of both the cultivation types inhibited the proliferation of Caco-2 cells in a concentrationdependent manner, with biodynamic strawberries exhibiting the highest antiproliferative activity. Biodynamic strawberries showed a markedly higher concentration of phenolic acids and slightly higher amounts of both quercetin and kaempferol compared with conventional strawberries. Although strawberries are an important vehicle of bioactive molecules, being a rich source of phenolic substances, a clear correlation between antiproliferative activity and these compounds or antioxidant activity was not observed. Studies to further characterize antioxidant/bioactive profiles in biodynamic strawberries compared with conventional strawberries are necessary to explain the observed differences in the antiproloferative capacity.
Archives of toxicology. Supplement. = Archiv für Toxikologie. Supplement
Before exerting a carcinogenic or mutagenic effect, many chemicals must undergo metabolic activat... more Before exerting a carcinogenic or mutagenic effect, many chemicals must undergo metabolic activation. The most widely used activation system is the 9,000 g supernatant fraction (S-9) of rat liver homogenate, prepared from male rats pretreated with Aroclor 1254 (AC). The present study compares the capabilities to induce metabolic activation of 2-aminofluorene (2-AF), using different sources of S-9 preparations as a test-promutagen, both in the Ames test and in the minimal saline liquid medium (MSLM). In particular, S-9 preparations of liver and kidney fractions from male rats and guinea pigs, with or without AC or phenobarbital (PB) pretreatment, were used. The 2-AF was tested in Salmonella typhimurium TA 1538 strain (frame-shift mutation) at different level of concentrations. In the Ames test the enzymatic activation of liver fractions, induced by PB, shows a large increase of mutagenicity of 2-AF in both animal species studied. The AC pretreatment in rats significantly reduced the mutagenic activity of 2-AF, when compared with controls. With rat renal microsomes no differences were observed in mutagenicity as compared with controls. A significant increase was seen in the microsomes of guinea pigs pretreated with AC. The experiments carried out with MSLM confirmed the results in full.
Archives of Industrial Hygiene and Toxicology, 2015
Individual sensitivity to ionising radiation (IR) is the result of interaction between exposure, ... more Individual sensitivity to ionising radiation (IR) is the result of interaction between exposure, DNA damage, and its repair, which is why polymorphisms in DNA repair genes could play an important role. We examined the association between DNA damage, expressed as micronuclei (MNi), nuclear buds (NBs), and nucleoplasmic bridges (NPBs) and single nucleotide polymorphisms in selected DNA repair genes (APE1, hOGG1, XRCC1, XRCC3, XPD, PARP1, MGMT genes; representative of the different DNA repair pathways operating in mammals) in 77 hospital workers chronically exposed to low doses of IR, and 70 matched controls. A significantly higher MNi frequency was found in the exposed group (16.2±10.4 vs. 11.5±9.4; P=0.003) and the effect appeared to be independent from the principal confounding factor. Exposed individuals with hOGG1, XRCC1, PARP1, and MGMT wild-type alleles or APEX1, as well as XPD (rs13181) heterozygous showed a significantly higher MNi frequency than controls with the same genotypes. Genetic polymorphism analysis and cytogenetic dosimetry have proven to be a powerful tool complementary to physical dosimetry in regular health surveillance programmes.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1987
Mutation Research/Environmental Mutagenesis and Related Subjects, 1989
Mutation Research/Genetic Toxicology, 1996
The purpose of this study was to assess the cytogenetic effects in vitro and in vivo of a commonl... more The purpose of this study was to assess the cytogenetic effects in vitro and in vivo of a commonly used fungicide, Metalaxyl. Chromosome damage in vitro, quantified by cultured human peripheral blood lymphocytes, demonstrated dose-related effects not associated with mitotic inhibition or cell death. Significant induction of chromosomal aberrations was observed with between 300 and 1000 micrograms/ml Metalaxyl in the absence of microsomal activation. Incubation in the presence of S9 mix produced less cytogenetic damage. Single i.p. injections of 75-300 mg/kg Metalaxyl had no effect on the frequency of micronuclei, detected in murine polychromatic erythrocytes. Micronuclei results were not compromised by direct evidence of cytotoxicity in the bone marrow of treated animals. The results in the present study indicated that genotoxicity of Metalaxyl was detected only in vitro and not in vivo. Available data reported that Metalaxyl was non-carcinogenic and gave negative results in a battery of genotoxicity tests. So, clastogenicity of Metalaxyl may not be evidence for DNA reactivity, but it may indicate alterations in cell homeostasis which are well implicated in the process of carcinogenesis.
![Research paper thumbnail of Corrigendum to “Protective effect of creatine against RNA damage” [Mutat. Res. 670 (2009) 59–67]](https://attachments.academia-assets.com/39710468/thumbnails/1.jpg)
](Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2010
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / m o l m u t C o m... more j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / m o l m u t C o m m u n i t y a d d r e s s : w w w . e l s e v i e r . c o m / l o c a t e / m u t r e s Corrigendum Corrigendum to "Protective effect of creatine against RNA damage" [Mutat. Res.
Advances in Environmental Control Technology: Health and Toxicology, 1997
European Journal of Medicinal Chemistry, Dec 8, 2011
Mutation Research Genetic Toxicology and Environmental Mutagenesis, Jun 17, 2010
-Caryophyllene is a bi-cyclic sesquiterpene that occurs in essential oils from several plants. A... more -Caryophyllene is a bi-cyclic sesquiterpene that occurs in essential oils from several plants. A variety of biological activities have been ascribed to this compound. In particular, it seems to possess anticarcinogenic properties, due to its capability to induce detoxifying enzymes or to enhance, in vitro and in vivo, the natural killer cell-induced cytotoxicity against tumours. Conversely, the knowledge on the DNAdamaging activity of the substance and its modulation is scanty. Therefore, in this study, we aimed at evaluating the capability of -caryophyllene to protect cultured human lymphocytes from the genotoxic damage induced by ethyl methanesulfonate (EMS) and colcemid (COL) in the micronucleus assay. To investigate the mechanisms of action of this sesquiterpene, the cultures were treated with the compound before (pre-treatment), during (co-treatment) and after (post-treatment) treatment with the mutagens.
Teratogenesis Carcinogenesis and Mutagenesis, 1984
This study was designed to investigate the effect of ether anesthesia in rats, before i.p. inject... more This study was designed to investigate the effect of ether anesthesia in rats, before i.p. injections to induce the mono-oxygenase enzyme system, on biochemical properties of liver S9 fractions. Aminopyrine N-demethylase and p-nitroanisole O-demethylase activity levels, their stability, and lipid peroxidation were determined in S9 fractions after etherization (about 1 min in ether vapor chamber daily for 3 consecutive days, before i.p. injections of Na-phenobarbital and /3-naphthoflavone) and compared with controls receiving the same injections without etherization. The activities were slightly (but not significatively) enhanced after this treatment, but stability was markedly and significatively greater after 1 h of incubation in the conditions of the liver microsomal assay (+ 14.8% and +74.7 %, respectively); lipid peroxidation was strongly and significatively depressed (-76.0%). Etherization sufficient to kill the animals on the 4th day resulted in equally active but less stable S9 fraction enzymes. Dimethylnitrosamine (as a standard premutagen) was assayed with the D7 strain of Saccharomyces cerevisiae using S9 fractions obtained from both anesthetized and nonanesthetized rats. According to biochemical data, results obtained with S9 from partially anesthetized rats were comparable with the conventional ones (S9 from nonanesthetized rats). On the contrary, the use of more prolonged ether anesthesia, including one on the day the animals are killed, gives S9 fraction significantly less effective.
Drugs under experimental and clinical research
The genotoxicity of nitroimidazoles and, in particular, their potential carcinogenicity has been ... more The genotoxicity of nitroimidazoles and, in particular, their potential carcinogenicity has been demonstrated. In order to investigate the specific target organ(s) for these drugs or their metabolites, a method for measuring mutations in microorganisms, with reference to the metabolism of mammals, was used in mice. Metronidazole and azanidazole were tested for their ability to induce genetic effects in a diploid strain (D7) of Saccharomyces cerevisiae in the Intrasanguineous Host-Mediated Assay. The test compounds showed dose-related increases of point mutation and mitotic gene conversion frequencies in liver, kidney and lung. Azanidazole seemed to favour the kidney and the liver, although increases in genotoxicity were observed also in the lung. Metronidazole was toxic and induced both point mutation and mitotic gene conversion when recovered from the liver. Yeast recovered from the kidney and the lung showed an increase especially in point mutation. This work provides more information about the mechanisms involved in the mutagenicity of nitroimidazoles at the site of action.
Anticancer research
Background: Little is known regarding the potentially chemopreventive activity of cyanidin-3-O-‚g... more Background: Little is known regarding the potentially chemopreventive activity of cyanidin-3-O-‚glucopyranoside (Cy-g), the main anthocyanin present in the juice of pigmented oranges, apart from its antioxidant activity. After excluding a potential genotoxicity of Cy-g, its ability to induce apoptosis on transformed and normal T cells was analysed. In order to delineate the events leading to apoptosis, the expression of different proteins, known to be involved in apoptosis, was also measured. Materials and Methods: The evaluation of genotoxicity was performed by the micronucleus test. Flow cytometry was used for the analysis of apoptotic cells and proteins involved in the modulation of apoptosis. Results: Cy-g was nongenotoxic. Moreover, it induced apoptosis in both cell systems, modulated by an increase of p53 and bax proteins. Conclusion: These interesting biological properties should encourage further studies into the chemopreventive potential of Cy-g. Nevertheless, its activity in normal T cells underlines the need for extensive toxicological investigation.
PloS one, 2015
Socio-economic, cultural and environmental factors are becoming increasingly important determinan... more Socio-economic, cultural and environmental factors are becoming increasingly important determinants of chronic obstructive pulmonary disease (COPD). We conducted a study to investigate socio-demographic, lifestyle and clinical factors, and to assess their role as predictors of acute events (mortality or hospitalization for respiratory causes) in a group of COPD patients. Subjects were recruited among outpatients who were undertaking respiratory function tests at the Pneumology Unit of the Sant'Orsola-Malpighi Hospital, Bologna. Patients were classified according to the GOLD Guidelines. 229 patients with COPD were included in the study, 44 with Mild, 68 Moderate, 52 Severe and 65 Very Severe COPD (GOLD stage). Significant differences among COPD stage, in terms of smoking status and fragility index, were detected. COPD stage significantly affected the values of all clinical tests (spirometry and ABG analysis). Kaplan-Meier estimates showed a significant difference between survival...
Toxicological Sciences, 2015
DNA sequence and genetic factors alone cannot fully explain the many processes implicated in dise... more DNA sequence and genetic factors alone cannot fully explain the many processes implicated in diseases initiation and development. It is now well understood that additional factors are involved in a final resulting phenotype. Epigenetic modifications, heritable changes not affecting the DNA sequence, are a key phenomenon at the basis of normal growth and differentiation. However, these can be defective leading to diseases, such as cancer. An increasing body of literature reports the environmental and occupational exposure to a mixture of natural and man-produced substances leading to epigenetic alterations. The identification of key genetic and/or epigenetic events involved in chemical carcinogenesis is an important step towards the discovery of biomarkers that can be used to evaluate the exposure, predict biological effects, and prevent adverse health consequences. Here, we focus on epidemiological studies to review the most recent advances in understanding genetic and epigenetic factors in relation to particulate matter, benzene and polycyclic aromatic hydrocarbons exposure.
Acta Horticulturae, 2010
The fruit characteristics, level of some phenolic compounds (phenolic acids, flavonols) and antio... more The fruit characteristics, level of some phenolic compounds (phenolic acids, flavonols) and antioxidant capacity were determined in strawberries (Fragaria ananassa L., 'Favette') grown by conventional and biodynamic agricultural methods. In addition, the in vitro bioactivity of biodynamic and conventional strawberry extracts, in terms of antiproliferative activities in human colon carcinoma (Caco-2) cells, was also evaluated. The strawberry extracts of both the cultivation types inhibited the proliferation of Caco-2 cells in a concentrationdependent manner, with biodynamic strawberries exhibiting the highest antiproliferative activity. Biodynamic strawberries showed a markedly higher concentration of phenolic acids and slightly higher amounts of both quercetin and kaempferol compared with conventional strawberries. Although strawberries are an important vehicle of bioactive molecules, being a rich source of phenolic substances, a clear correlation between antiproliferative activity and these compounds or antioxidant activity was not observed. Studies to further characterize antioxidant/bioactive profiles in biodynamic strawberries compared with conventional strawberries are necessary to explain the observed differences in the antiproloferative capacity.
Archives of toxicology. Supplement. = Archiv für Toxikologie. Supplement
Before exerting a carcinogenic or mutagenic effect, many chemicals must undergo metabolic activat... more Before exerting a carcinogenic or mutagenic effect, many chemicals must undergo metabolic activation. The most widely used activation system is the 9,000 g supernatant fraction (S-9) of rat liver homogenate, prepared from male rats pretreated with Aroclor 1254 (AC). The present study compares the capabilities to induce metabolic activation of 2-aminofluorene (2-AF), using different sources of S-9 preparations as a test-promutagen, both in the Ames test and in the minimal saline liquid medium (MSLM). In particular, S-9 preparations of liver and kidney fractions from male rats and guinea pigs, with or without AC or phenobarbital (PB) pretreatment, were used. The 2-AF was tested in Salmonella typhimurium TA 1538 strain (frame-shift mutation) at different level of concentrations. In the Ames test the enzymatic activation of liver fractions, induced by PB, shows a large increase of mutagenicity of 2-AF in both animal species studied. The AC pretreatment in rats significantly reduced the mutagenic activity of 2-AF, when compared with controls. With rat renal microsomes no differences were observed in mutagenicity as compared with controls. A significant increase was seen in the microsomes of guinea pigs pretreated with AC. The experiments carried out with MSLM confirmed the results in full.
Archives of Industrial Hygiene and Toxicology, 2015
Individual sensitivity to ionising radiation (IR) is the result of interaction between exposure, ... more Individual sensitivity to ionising radiation (IR) is the result of interaction between exposure, DNA damage, and its repair, which is why polymorphisms in DNA repair genes could play an important role. We examined the association between DNA damage, expressed as micronuclei (MNi), nuclear buds (NBs), and nucleoplasmic bridges (NPBs) and single nucleotide polymorphisms in selected DNA repair genes (APE1, hOGG1, XRCC1, XRCC3, XPD, PARP1, MGMT genes; representative of the different DNA repair pathways operating in mammals) in 77 hospital workers chronically exposed to low doses of IR, and 70 matched controls. A significantly higher MNi frequency was found in the exposed group (16.2±10.4 vs. 11.5±9.4; P=0.003) and the effect appeared to be independent from the principal confounding factor. Exposed individuals with hOGG1, XRCC1, PARP1, and MGMT wild-type alleles or APEX1, as well as XPD (rs13181) heterozygous showed a significantly higher MNi frequency than controls with the same genotypes. Genetic polymorphism analysis and cytogenetic dosimetry have proven to be a powerful tool complementary to physical dosimetry in regular health surveillance programmes.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 1987
Mutation Research/Environmental Mutagenesis and Related Subjects, 1989
Mutation Research/Genetic Toxicology, 1996
The purpose of this study was to assess the cytogenetic effects in vitro and in vivo of a commonl... more The purpose of this study was to assess the cytogenetic effects in vitro and in vivo of a commonly used fungicide, Metalaxyl. Chromosome damage in vitro, quantified by cultured human peripheral blood lymphocytes, demonstrated dose-related effects not associated with mitotic inhibition or cell death. Significant induction of chromosomal aberrations was observed with between 300 and 1000 micrograms/ml Metalaxyl in the absence of microsomal activation. Incubation in the presence of S9 mix produced less cytogenetic damage. Single i.p. injections of 75-300 mg/kg Metalaxyl had no effect on the frequency of micronuclei, detected in murine polychromatic erythrocytes. Micronuclei results were not compromised by direct evidence of cytotoxicity in the bone marrow of treated animals. The results in the present study indicated that genotoxicity of Metalaxyl was detected only in vitro and not in vivo. Available data reported that Metalaxyl was non-carcinogenic and gave negative results in a battery of genotoxicity tests. So, clastogenicity of Metalaxyl may not be evidence for DNA reactivity, but it may indicate alterations in cell homeostasis which are well implicated in the process of carcinogenesis.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2010
j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / m o l m u t C o m... more j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / m o l m u t C o m m u n i t y a d d r e s s : w w w . e l s e v i e r . c o m / l o c a t e / m u t r e s Corrigendum Corrigendum to "Protective effect of creatine against RNA damage" [Mutat. Res.