478 results on '"Bignami, Margherita"'
Search Results
152. The Mammalian Mismatch Repair Pathway Removes DNA 8-oxodGMP Incorporated from the Oxidized dNTP Pool
- Author
-
Colussi, Claudia, primary, Parlanti, Eleonora, additional, Degan, Paolo, additional, Aquilina, Gabriele, additional, Barnes, Deborah, additional, Macpherson, Peter, additional, Karran, Peter, additional, Crescenzi, Marco, additional, Dogliotti, Eugenia, additional, and Bignami, Margherita, additional
- Published
- 2002
- Full Text
- View/download PDF
153. Human MRE11 is inactivated in mismatch repair‐deficient cancers
- Author
-
Giannini, Giuseppe, primary, Ristori, Elisabetta, additional, Cerignoli, Fabio, additional, Rinaldi, Christian, additional, Zani, Massimo, additional, Viel, Alessandra, additional, Ottini, Laura, additional, Crescenzi, Marco, additional, Martinotti, Stefano, additional, Bignami, Margherita, additional, Frati, Luigi, additional, Screpanti, Isabella, additional, and Gulino, Alberto, additional
- Published
- 2002
- Full Text
- View/download PDF
154. Mismatch repair in correction of replication errors and processing of DNA damage
- Author
-
Aquilina, Gabriele, primary and Bignami, Margherita, additional
- Published
- 2001
- Full Text
- View/download PDF
155. Sensitivity to DNA cross-linking chemotherapeutic agents in mismatch repair-defective cellsin vitro and in xenografts
- Author
-
Fiumicino, Silvia, primary, Martinelli, Simone, additional, Colussi, Claudia, additional, Aquilina, Gabriele, additional, Leonetti, Carlo, additional, Crescenzi, Marco, additional, and Bignami, Margherita, additional
- Published
- 2000
- Full Text
- View/download PDF
156. Mismatch repair, G 2 /M cell cycle arrest and lethality after DNA damage
- Author
-
Aquilina, Gabriele, primary, Crescenzi, Marco, additional, and Bignami, Margherita, additional
- Published
- 1999
- Full Text
- View/download PDF
157. Effect of hMSH6 cDNA expression on the phenotype of mismatch repair-deficient colon cancer cell line HCT15
- Author
-
Lettieri, Teresa, primary, Marra, Giancarlo, additional, Aquilina, Gabriele, additional, Bignami, Margherita, additional, Crompton, Nigel E.A., additional, Palombo, Fabio, additional, and Jiricny, Josef, additional
- Published
- 1999
- Full Text
- View/download PDF
158. Increased somatic recombination in methylation tolerant human cells with defective DNA mismatch repair
- Author
-
Ciotta, Carmela, primary, Ceccotti, Sabrina, additional, Aquilina, Gabriele, additional, Humbert, Odile, additional, Palombo, Fabio, additional, Jiricny, Josef, additional, and Bignami, Margherita, additional
- Published
- 1998
- Full Text
- View/download PDF
159. Reversal of methylation tolerance by transfer of human chromosome 2
- Author
-
Aquilina, Gabriele, primary, Fiumicino, Silvia, additional, Zijno, Andrea, additional, Martinelli, Simone, additional, Overkamp, Wilhelmina J.I, additional, Zdzienicka, Malgorzata Z, additional, Oshimura, Mitsuo, additional, Wild, Chris P, additional, and Bignami, Margherita, additional
- Published
- 1997
- Full Text
- View/download PDF
160. P III A.9 Increased somatic recombination in methylation tolerant human cells with defective mismatch repair
- Author
-
Ciotta, Carmela, primary, Ceccotti, Sabrina, additional, Aquilina, Gabriele, additional, Palombo, Fabio, additional, Jiricny, Josef, additional, Humbert, Odile, additional, and Bignami, Margherita, additional
- Published
- 1997
- Full Text
- View/download PDF
161. P III A.8 Sensitivity to CCNU in methylation tolerant mismatch repair defective human cells
- Author
-
Aquilina, Gabriele, primary, Ceccotti, Sabrina, additional, Martinelli, Simone, additional, Hampson, Richard, additional, and Bignami, Margherita, additional
- Published
- 1997
- Full Text
- View/download PDF
162. Processing of O6-methylguanine by mismatch correction in human cell extracts
- Author
-
Ceccotti, Sabrina, primary, Aquilina, Gabriele, additional, Macpherson, Peter, additional, Yamada, Masami, additional, Karran, Peter, additional, and Bignami, Margherita, additional
- Published
- 1996
- Full Text
- View/download PDF
163. Drug-related killings: a case of mistaken identity
- Author
-
Karran, Peter, primary and Bignami, Margherita, additional
- Published
- 1996
- Full Text
- View/download PDF
164. Mutation analysis in two newly identified rat p53 pseudogenes
- Author
-
Ciotta, Carmela, primary, Dogliotti, Eugenia, additional, and Bignami, Margherita, additional
- Published
- 1995
- Full Text
- View/download PDF
165. Multiple mutations and frameshifts are the hallmark of defective hPMS2 in pZ189-transfected human tumor cells.
- Author
-
Ceccotti, Sabrina, Ciotta, Carmela, Fronza, Gilberto, Dogliotti, Eugenia, and Bignami, Margherita
- Published
- 2000
- Full Text
- View/download PDF
166. Sensitivity to DNA cross-linking chemotherapeutic agents in mismatch repair-defective cells in vitro and in xenografts.
- Author
-
Fiumicino, Silvia, Martinelli, Simone, Colussi, Claudia, Aquilina, Gabriele, Leonetti, Carlo, Crescenzi, Marco, and Bignami, Margherita
- Published
- 2000
- Full Text
- View/download PDF
167. Mismatch repair, G2/M cell cycle arrest and lethality after DNA damage.
- Author
-
Aquilina, Gabriele, Crescenzi, Marco, and Bignami, Margherita
- Abstract
The role of the mismatch repair pathway in DNA replication is well defined but its involvement in processing DNA damage induced by chemical or physical agents is less clear. DNA repair and cell cycle control are tightly linked and it has been suggested that mismatch repair is necessary to activate the G2/M checkpoint in the presence of certain types of DNA damage. We investigated the proposed role for mismatch repair (MMR) in activation of the G2/M checkpoint following exposure to DNA-damaging agents. We compared the response of MMR-proficient HeLa and Raji cells with isogenic variants defective in either the hMutLα or hMutSα complex. Different agents were used: the cross-linker N-(2-chloroethyl)-N′-cyclohexyl-N-nitrosourea (CCNU), γ-radiation and the monofunctional methylating agent N-methyl-N-nitrosourea (MNU). MMR-defective cells are relatively sensitive to CCNU, while no differences in survival between repair-proficient and -deficient cells were observed after exposure to γ-radiation. Analysis of cell cycle distribution indicates that G2 arrest is induced at least as efficiently in MMR-defective cells after exposure to either CCNU or ionizing radiation. As expected, MNU does not induce G2 accumulation in MMR-defective cells, which are known to be highly tolerant to killing by methylating agents, indicating that MNU-induced cell cycle alterations are strictly dependent on the cytotoxic processing of methylation damage by MMR. Conversely, activation of the G2/M checkpoint after DNA damage induced by CCNU and γ-radiation does not depend on functional MMR. In addition, the absence of a simple correlation between the extent of G2 arrest and cell killing by these agents suggests that G2 arrest reflects the processing by MMR of both lethal and non-lethal DNA damage. [ABSTRACT FROM PUBLISHER]
- Published
- 1999
- Full Text
- View/download PDF
168. Mutagenicity of chemicals of industrial and agricultural relevance in Salmonella, streptomyces and Aspergillus.
- Author
-
Principe, Paola, Dogliotti, Eugenia, Bignami, Margherita, Crebelli, Riccardo, Falcone, Emiliana, Fabrizi, Maria, Conti, Giuseppe, and Comba, Pietro
- Published
- 1981
- Full Text
- View/download PDF
169. Specific viral oncogenes cause differential effects on cell-to-cell communication, relevant to the suppression of the transformed phenotype by normal cells.
- Author
-
Bignami, Margherita, Rosa, Silvia, Falcone, Germana, Tató, Franco, Katoh, Fumitaka, and Yamasaki, Hiroshi
- Published
- 1988
- Full Text
- View/download PDF
170. Spontaneous mutations at aprt locus in a mammalian cell line defective in mismatch recognition.
- Author
-
Hess, Patricia, Aquilina, Gabriele, Dogliotti, Eugenia, and Bignami, Margherita
- Published
- 1994
- Full Text
- View/download PDF
171. Tumor Promoters Enhance v-myc-induced Focus Formation in Mammalian Cell Linesa.
- Author
-
BIGNAMI, MARGHERITA, ROSA, SILVIA, ROCCA, SEVERINA ANNA, FALCONE, GERMANA, and TATÒ, FRANCO
- Published
- 1987
- Full Text
- View/download PDF
172. Mutagenesis and morphological transformation by N-methyl-N′-nitro-N-nitrosoguanidine in the BALB/3T3 clone A31-1-1 cell line.
- Author
-
Bignami, Margherita and Saffiotti, Umberto
- Abstract
Concomitant induction of ouabain resistant mutations and morphological transformation in the BALB/3T3 ClA31-1-1-c mouse embryo cell line were obtained after a 30 min treatment with the direct alkylating agent -methyl-′-nitro--nitrosoguanidine (MNNG). Parameters affecting mutation frequencies were determined. The optimal expression time (48 h) for ouabain resistance was independent from the dose of the carcinogen. A linear dose-response relationship for mutation induction was found after treatment with increasing doses of MNNG. The ratio of malignant transformation to mutation frequencies induced by the short treatment with MNNG was found to be within the same order of magnitude over a four-fold dose range. The development of a mutational assay for ouabain resistance in the BALB/3T3 ClA31-1-1-c cell line makes quantitative comparisons possible between mutation and neoplastic transformation frequencies induced by chemical carcinogens in this single cellular system. [ABSTRACT FROM PUBLISHER]
- Published
- 1983
173. Studies on Chemically Induced Neoplastic Transformation and Mutation in the BALB/3T3 Cl A31-1-1 Cell Line in Relation to the Quantitative Evaluation of Carcinogens.
- Author
-
Saffiotti, Umberto, Bignami, Margherita, Bertolero, Federico, Cortesi, Enrico, Ficorella, Corrado, and Kaighn, M. Edward
- Published
- 1984
- Full Text
- View/download PDF
174. Sensitivity to DNA cross-linking chemotherapeutic agents in mismatch repair-defective cells <TOGGLE>in vitro</TOGGLE> and in xenografts
- Author
-
Fiumicino, Silvia, Martinelli, Simone, Colussi, Claudia, Aquilina, Gabriele, Leonetti, Carlo, Crescenzi, Marco, and Bignami, Margherita
- Abstract
Together with tolerance to killing induced by methylating agents, loss of mismatch repair (MMR) has previously been found to be associated with hypersensitivity to the DNAcross-linking agent 1-(2-chloroethyl)-3-cyclohexyl-nitrosourea(CCNU) in several human tumor cell lines (Aquilina et al.,
1998 ). Here, we have investigated whether MMR might act as an efficient repair pathway and provide protection against the clastogenicity induced by CCNU and whether the hypersensitivity of MMR-defective cells is extended to other cross-linking agents. An increase in cell killing and in the frequency of micronuclei was observed after CCNU exposure in 2 hPMS2-defective clones (clones 6 and 7) compared with the parental HeLa cells. Introduction of a wild-type copy of chromosome 7 in clone 7 led to re-expression of the hPMS2 protein and brought survival and chromosomal damage upon CCNU exposure to parental levels. Our data indicate that MMR protects against the clastogenic damage induced by this drug. The hPMS2-defective HeLa cells were also hypersensitive to killing by mitomycin C. Mitomycin C sensitivity was confirmed in an hMLH1-defective clone derived from Raji cells and in msh2-defective mouse embryo fibroblasts derived from knock-out mice. hPMS2-defective and parental HeLa cells were transplanted into nude mice, and the animals were treated with mitomycin C. While parental cell growth rate was unaffected, the growth of MMR-defective tumor was significantly reduced. Our results indicate that the in vitro hypersensitivity to mitomycin C conferred by loss of MMR is paralleled in vivo and may have implications for the chemotherapy of MMR-defective tumors. Int. J. Cancer 85:590596, 2000. © 2000 Wiley-Liss, Inc.- Published
- 2000
- Full Text
- View/download PDF
175. Evaluation of calcium lignosulfonate as a acceptable previous cargo for edible fats and oils.
- Author
-
Schrenk, Dieter, Bignami, Margherita, Bodin, Laurent, Chipman, James Kevin, del Mazo, Jesús, Grasl‐Kraupp, Bettina, Hogstrand, Christer, Hoogenboom, Laurentius (Ron), Leblanc, Jean‐Charles, Nebbia, Carlo Stefano, Nielsen, Elsa, Ntzani, Evangelia, Petersen, Annette, Sand, Salomon, Schwerdtle, Tanja, Wallace, Heather, Grob, Konrad, Castle, Laurence, Christodoulidou, Anna, and Vleminckx, Christiane
- Subjects
- *
EDIBLE fats & oils , *FREIGHT & freightage , *FATS & oils , *CALCIUM , *CARGO ships - Abstract
Shipping of edible fats and oils into Europe is permitted in bulk tanks, provided that the previous cargo is included in a positive list. The European Commission requested EFSA to evaluate the acceptability of calcium lignosulfonate as previous cargo for fats and oils. The evaluation was based on the same criteria as those used for the evaluation of the substances currently on the list in the Annex to Commission Directive 96/3/EC as a acceptable previous cargoes for edible fats and oils. In 2017, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) concluded that calcium lignosulfonate did not meet the acceptability criteria, due to uncertainties as regards the composition and toxicity of its low‐molecular weight fraction (LMWF) below 1,000 Da. In the current evaluation, new information, showing lack of genotoxicity of the LMWF isolated from a technical grade of calcium lignosulfonate was provided. Due to uncertainties regarding the presence of lignosulfonate components below 200 Da in this LMWF tested for genotoxicity, the CONTAM Panel concluded that the information provided was insufficient to assess the acceptability of calcium lignosulfonate as previous cargo. The Panel recommends a better analysis of the LMWF and a new genotoxicity test using this LMWF, including components < 200 Da, and evidence that the tested material is representative of the LMWF in products intended to be shipped as previous cargo for edible fat and oils. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
176. Evaluation of the health risks related to the presence of cyanogenic glycosides in foods other than raw apricot kernels.
- Author
-
Schrenk, Dieter, Bignami, Margherita, Bodin, Laurent, Chipman, James Kevin, del Mazo, Jesús, Grasl‐Kraupp, Bettina, Hogstrand, Christer, Hoogenboom, Laurentius (Ron), Leblanc, Jean‐Charles, Nebbia, Carlo Stefano, Nielsen, Elsa, Ntzani, Evangelia, Petersen, Annette, Sand, Salomon, Vleminckx, Christiane, Wallace, Heather, Benford, Diane, Brimer, Leon, Mancini, Francesca Romana, and Metzler, Manfred
- Subjects
- *
GLYCOSIDES , *APRICOT , *CYANIDES , *BIOAVAILABILITY , *BISCUITS - Abstract
In 2016, the EFSA Panel on Contaminants in the Food Chain (CONTAM) published a scientific opinion on the acute health risks related to the presence of cyanogenic glycosides (CNGs) in raw apricot kernels in which an acute reference dose (ARfD) of 20 μg/kg body weight (bw) was established for cyanide (CN). In the present opinion, the CONTAM Panel concluded that this ARfD is applicable for acute effects of CN regardless the dietary source. To account for differences in cyanide bioavailability after ingestion of certain food items, specific factors were used. Estimated mean acute dietary exposures to cyanide from foods containing CNGs did not exceed the ARfD in any age group. At the 95th percentile, the ARfD was exceeded up to about 2.5‐fold in some surveys for children and adolescent age groups. The main contributors to exposures were biscuits, juice or nectar and pastries and cakes that could potentially contain CNGs. Taking into account the conservatism in the exposure assessment and in derivation of the ARfD, it is unlikely that this estimated exceedance would result in adverse effects. The limited data from animal and human studies do not allow the derivation of a chronic health‐based guidance value (HBGV) for cyanide, and thus, chronic risks could not be assessed. This publication is linked to the following EFSA Supporting Publications article: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2019.EN-1601/full [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
177. Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food.
- Author
-
Knutsen, Helle Katrine, Alexander, Jan, Barregård, Lars, Bignami, Margherita, Brüschweiler, Beat, Ceccatelli, Sandra, Cottrill, Bruce, Dinovi, Michael, Edler, Lutz, Grasl‐Kraupp, Bettina, Hogstrand, Christer, Hoogenboom, Laurentius (Ron), Nebbia, Carlo Stefano, Oswald, Isabelle P, Petersen, Annette, Rose, Martin, Roudot, Alain‐Claude, Vleminckx, Christiane, Vollmer, Günter, and Wallace, Heather
- Subjects
PERFLUOROOCTANE sulfonate ,PERFLUOROOCTANOIC acid ,GASTROINTESTINAL system ,METABOLISM ,CHOLESTEROL - Abstract
The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in food. Regarding PFOS and PFOA occurrence, the final data set available for dietary exposure assessment contained a total of 20,019 analytical results (PFOS n = 10,191 and PFOA n = 9,828). There were large differences between upper and lower bound exposure due to analytical methods with insufficient sensitivity. The CONTAM Panel considered the lower bound estimates to be closer to true exposure levels. Important contributors to the lower bound mean chronic exposure were 'Fish and other seafood', 'Meat and meat products' and 'Eggs and egg products', for PFOS, and 'Milk and dairy products', 'Drinking water' and 'Fish and other seafood' for PFOA. PFOS and PFOA are readily absorbed in the gastrointestinal tract, excreted in urine and faeces, and do not undergo metabolism. Estimated human half‐lives for PFOS and PFOA are about 5 years and 2–4 years, respectively. The derivation of a health‐based guidance value was based on human epidemiological studies. For PFOS, the increase in serum total cholesterol in adults, and the decrease in antibody response at vaccination in children were identified as the critical effects. For PFOA, the increase in serum total cholesterol was the critical effect. Also reduced birth weight (for both compounds) and increased prevalence of high serum levels of the liver enzyme alanine aminotransferase (ALT) (for PFOA) were considered. After benchmark modelling of serum levels of PFOS and PFOA, and estimating the corresponding daily intakes, the CONTAM Panel established a tolerable weekly intake (TWI) of 13 ng/kg body weight (bw) per week for PFOS and 6 ng/kg bw per week for PFOA. For both compounds, exposure of a considerable proportion of the population exceeds the proposed TWIs. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
178. Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food.
- Author
-
Knutsen, Helle Katrine, Alexander, Jan, Barregård, Lars, Bignami, Margherita, Brüschweiler, Beat, Ceccatelli, Sandra, Cottrill, Bruce, Dinovi, Michael, Edler, Lutz, Grasl‐Kraupp, Bettina, Hogstrand, Christer, Nebbia, Carlo Stefano, Oswald, Isabelle P, Petersen, Annette, Rose, Martin, Roudot, Alain‐Claude, Schwerdtle, Tanja, Vleminckx, Christiane, Vollmer, Günter, and Wallace, Heather
- Subjects
DIOXINS ,FOOD ,ANIMAL feeds ,FOOD safety ,SEMEN analysis - Abstract
The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL‐PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre‐ and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO2005‐TEQ/g fat in blood sampled at age 9 years based on PCDD/F‐TEQs. No association was observed when including DL‐PCB‐TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F‐TEQ only was on average 2.4‐ and 2.7‐fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL‐PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk. This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2018.EN-1136/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2018.EN-1137/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2018.EN-1374/full [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
179. The MUTYH base excision repair gene protects against inflammation-associated colorectal carcinogenesis
- Author
-
Grasso, Francesca, Di Meo, Serena, Luca, Gabriele, Pasquini, Luca, Stefania Rossi, Boirivant, Monica, Biffoni, Mauro, Bignami, Margherita, and Di Carlo, Emma
180. Isolation of mutants unable to reduce nitrate by co-mutation in Streptomyces coelicolor.
- Author
-
ORTALI, VITTORIA, primary, ALBANO, GABRIELLA, additional, CREBELLI, RICCARDO, additional, BIGNAMI, MARGHERITA, additional, and CARERE, ANGELO, additional
- Published
- 1980
- Full Text
- View/download PDF
181. Non-disjunction and crossing-over induced by pharmaceutical drugs in Aspergillus nidulans
- Author
-
Bignami, Margherita, primary, Morpurgo, Giorgio, additional, Pagliani, Rossella, additional, Carere, Angelo, additional, Conti, Giuseppe, additional, and Di Giuseppe, Gennaro, additional
- Published
- 1974
- Full Text
- View/download PDF
182. Genotoxic activity of dichlorvos, trichlorfon and dichloroacetaldehyde
- Author
-
Aquilina, Gabriele, primary, Benigni, Romualdo, additional, Bignami, Margherita, additional, Calcagnile, Angelo, additional, Dogliotti, Eugenia, additional, Falcone, Emiliana, additional, and Carere, Angelo, additional
- Published
- 1984
- Full Text
- View/download PDF
183. Comutation in Streptomyces
- Author
-
Randazzo, Rosalba, primary, Sermonti, Giuseppe, additional, Carere, Angelo, additional, and Bignami, Margherita, additional
- Published
- 1973
- Full Text
- View/download PDF
184. Risk to human and animal health related to the presence of 4,15‐diacetoxyscirpenol in food and feed.
- Author
-
Knutsen, Helle Katrine, Alexander, Jan, Barregård, Lars, Bignami, Margherita, Brüschweiler, Beat, Ceccatelli, Sandra, Cottrill, Bruce, Dinovi, Michael, Grasl‐Kraupp, Bettina, Hogstrand, Christer, Hoogenboom, Laurentius (Ron), Nebbia, Carlo Stefano, Oswald, Isabelle P, Petersen, Annette, Rose, Martin, Roudot, Alain‐Claude, Schwerdtle, Tanja, Vleminckx, Christiane, Vollmer, Günter, and Wallace, Heather
- Published
- 2018
- Full Text
- View/download PDF
185. Re‐evaluation of the risks to public health related to the presence of bisphenol A (BPA) in foodstuffs.
- Author
-
Lambré, Claude, Barat Baviera, José Manuel, Bolognesi, Claudia, Chesson, Andrew, Cocconcelli, Pier Sandro, Crebelli, Riccardo, Gott, David Michael, Grob, Konrad, Lampi, Evgenia, Mengelers, Marcel, Mortensen, Alicja, Rivière, Gilles, Silano, Vittorio, Steffensen, Inger‐Lise, Tlustos, Christina, Vernis, Laurence, Zorn, Holger, Batke, Monika, Bignami, Margherita, and Corsini, Emanuela
- Subjects
- *
T helper cells , *PUBLIC health , *PNEUMONIA , *AGE groups , *BODY weight , *ANIMAL welfare laws - Abstract
In 2015, EFSA established a temporary tolerable daily intake (t‐TDI) for BPA of 4 μg/kg body weight (bw) per day. In 2016, the European Commission mandated EFSA to re‐evaluate the risks to public health from the presence of BPA in foodstuffs and to establish a tolerable daily intake (TDI). For this re‐evaluation, a pre‐established protocol was used that had undergone public consultation. The CEP Panel concluded that it is Unlikely to Very Unlikely that BPA presents a genotoxic hazard through a direct mechanism. Taking into consideration the evidence from animal data and support from human observational studies, the immune system was identified as most sensitive to BPA exposure. An effect on Th17 cells in mice was identified as the critical effect; these cells are pivotal in cellular immune mechanisms and involved in the development of inflammatory conditions, including autoimmunity and lung inflammation. A reference point (RP) of 8.2 ng/kg bw per day, expressed as human equivalent dose, was identified for the critical effect. Uncertainty analysis assessed a probability of 57–73% that the lowest estimated Benchmark Dose (BMD) for other health effects was below the RP based on Th17 cells. In view of this, the CEP Panel judged that an additional uncertainty factor (UF) of 2 was needed for establishing the TDI. Applying an overall UF of 50 to the RP, a TDI of 0.2 ng BPA/kg bw per day was established. Comparison of this TDI with the dietary exposure estimates from the 2015 EFSA opinion showed that both the mean and the 95th percentile dietary exposures in all age groups exceeded the TDI by two to three orders of magnitude. Even considering the uncertainty in the exposure assessment, the exceedance being so large, the CEP Panel concluded that there is a health concern from dietary BPA exposure. This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.p210401/full [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
186. Targeting mismatch repair: a challenge for personalized chemotherapy.
- Author
-
Pichierri, Pietro and Bignami, Margherita
- Subjects
TUMOR treatment ,DNA damage ,DNA replication ,BIOCHEMICAL genetics ,DNA synthesis ,MOLECULAR genetics - Abstract
Mismatch repair (MMR) is the major repair pathway for removal of errors occurring during replication, which is often inactive in human tumours. Because MMR can control the cellular response to the cytotoxic effects of some DNA damaging drugs, here we will discuss how the MMR status can influence the biological response to chemotherapy. In addition we illustrate how some features of MMR-defective tumours might be exploited for personalized therapy treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
187. 8-Oxoguanine incorporation into DNA repeats in vitro and mismatch recognition by MutSα.
- Author
-
Macpherson, Peter, Barone, Flavia, Maga, Giovanni, Mazzei, Filomena, Karran, Peter, and Bignami, Margherita
- Published
- 2005
- Full Text
- View/download PDF
188. Evaluation of the shucking of certain species of scallops contaminated with lipophilic toxins with a view to the production of edible parts meeting the safety requirements foreseen in the Union legislation
- Author
-
EFSA Panel on Contaminants in the Food Chain (CONTAM), Dieter Schrenk, Margherita Bignami, Laurent Bodin, Jesús del Mazo, Bettina Grasl‐Kraupp, Christer Hogstrand, Kevin James Chipman, Jean‐Charles Leblanc, Carlo Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Ana Gago Martinez, Arjen Gerssen, Aurelia Tubaro, Claudia Cascio, José Cortiñas Abrahantes, Hans Steinkellner, Laurentius (Ron) Hoogenboom, European Commission, Schrenk, Dieter, Bignami, Margherita, Bodin, Laurent, Del Mazo, Jesús, Grasl-Kraupp, Bettina, Hogstrand, Christer, Leblanc, Jean-Charles, Nielsen, Elsa, Ntzani, Evangelia, Petersen, Annette, Sand, Salomon, Schwerdtle, Tanja, Vleminckx, Christiane, Gago Martínez, Ana, Gerssen, Arjen, Tubaro, Aurelia, Cascio, Claudia, Cortiñas Abrahantes, José, Hoogenboom, Laurentius (Ron), Schrenk, D., Bignami, M., Bodin, L., del Mazo, J., Grasl-Kraupp, B., Hogstrand, C., Chipman, K. J., Leblanc, J. -C., Nebbia, C. S., Nielsen, E., Ntzani, E., Petersen, A., Sand, S., Schwerdtle, T., Vleminckx, C., Wallace, H., Martinez, A. G., Gerssen, A., Tubaro, A., Cascio, C., Abrahantes, J. C., Steinkellner, H., Hoogenboom, L., Schrenk, Dieter [0000-0002-7717-5533], Bignami, Margherita [0000-0002-1525-6864], Bodin, Laurent [0000-0001-5671-3139], Del Mazo, Jesús [0000-0003-3269-3895], Grasl-Kraupp, Bettina [0000-0003-4889-6531], Hogstrand, Christer [0000-0001-7545-6975], Leblanc, Jean-Charles [0000-0003-2872-3414], Nielsen, Elsa [0000-0002-6874-2575], Ntzani, Evangelia [0000-0003-3712-4181], Petersen, Annette [0000-0003-3996-2701], Sand, Salomon [0000-0002-3360-0534], Schwerdtle, Tanja [0000-0002-4873-7488], Vleminckx, Christiane [0000-0002-9928-1601], Gago Martínez, Ana [0000-0001-5178-2338], Gerssen, Arjen [0000-0003-4271-1516], Tubaro, Aurelia [0000-0003-2773-2589], Cascio, Claudia [0000-0002-3810-4134], Cortiñas Abrahantes, José [0000-0002-4805-9429], and Hoogenboom, Laurentius (Ron) [0000-0002-8913-5328]
- Subjects
scallops ,Project- en Accountmanagement ,040301 veterinary sciences ,Veterinary (miscellaneous) ,BU Contaminanten & Toxines ,lipophilic marine biotoxin ,Team Toxicology ,TP1-1185 ,Plant Science ,010501 environmental sciences ,yessotoxins ,01 natural sciences ,Microbiology ,0403 veterinary science ,BU Contaminants & Toxins ,okadaic acid ,TX341-641 ,0105 earth and related environmental sciences ,VLAG ,azaspiracids ,Nutrition. Foods and food supply ,Chemical technology ,04 agricultural and veterinary sciences ,Team Natural Toxins ,azaspiracid ,shucking ,scallop ,Scientific Opinion ,Animal Science and Zoology ,Parasitology ,lipophilic marine biotoxins ,Food Science - Abstract
66 p.-22 fig.-18 tab-Appendix A-B (45-65), EFSA was asked by the European Commission to provide information on levels of lipophilic shellfish toxins in whole scallops that would ensure levels in edible parts below the regulatory limits after shucking, i.e. removal of non‐edible parts. This should include the okadaic acid (OA), the azaspiracid (AZA) and the yessotoxin (YTX) groups, and five species of scallops. In addition, EFSA was asked to recommend the number of scallops in an analytical sample. To address these questions, EFSA received suitable data on the three toxin groups in two scallop species, Aequipecten opercularis and Pecten maximus, i.e. data on individual and pooled samples of edible and non‐edible parts from contamination incidents. The majority of the concentration levels were below limit of quantification (LOQ)/limit of detection (LOD), especially in adductor muscle but also in gonads. Shucking in most cases resulted in a strong decrease in the toxin levels. For Pecten maximus, statistical analysis showed that levels in whole scallops should not exceed 256 μg OA eq/kg or 217 μg AZA1 eq/kg to ensure that levels in gonads are below the regulatory limits of 160 μg OA or AZA1 eq/kg with 99% certainty. Such an analysis was not possible for yessotoxins or any toxin in Aequipecten opercularis and an assessment could only be based on upper bound levels. To ensure a 95% correct prediction on whether the level in scallops in an area or lot is correctly predicted to be compliant/non‐compliant, it was shown that 10 scallops per sample would be sufficient to predict with 95% certainty if levels of OA‐group toxins in the area/lot were 25% below or above the regulatory limit. However, to predict with a 95% certainty for levels between 140 and 180 μg OA eq/kg, a pooled sample of more than 30 scallops would have to be tested.
- Published
- 2021
189. Young transgenic hMTH1 mice are protected against dietary fat‐induced metabolic stress—implications for enhanced longevity.
- Author
-
Marcon, Francesca, Meschini, Roberta, Iorio, Egidio, Palleschi, Simonetta, De Luca, Gabriele, Siniscalchi, Ester, Conti, Luigi, Chirico, Mattea, Pisanu, Maria Elena, De Battistis, Francesca, Rossi, Barbara, Minoprio, Anna, Giuliani, Alessandro, Karran, Peter, and Bignami, Margherita
- Subjects
- *
TRANSGENIC mice , *WEIGHT gain , *LONGEVITY , *GENE expression , *FAT , *HIGH-fat diet , *DNA damage , *OXIDATIVE stress - Abstract
hMTH1 protects against mutation during oxidative stress. It degrades 8‐oxodGTP to exclude potentially mutagenic oxidized guanine from DNA. hMTH1 expression is linked to ageing. Its downregulation in cultured cells accelerates RAS‐induced senescence, and its overexpression in hMTH1‐Tg mice extends lifespan. In this study, we analysed the effects of a brief (5 weeks) high‐fat diet challenge (HFD) in young (2 months old) and adult (7 months old) wild‐type (WT) and hMTH1‐Tg mice. We report that at 2 months, hMTH1 overexpression ameliorated HFD‐induced weight gain, changes in liver metabolism related to mitochondrial dysfunction and oxidative stress. It prevented DNA damage as quantified by a comet assay. At 7 months old, these HFD‐induced effects were less severe and hMTH1‐Tg and WT mice responded similarly. hMTH1 overexpression conferred lifelong protection against micronucleus induction, however. Since the canonical activity of hMTH1 is mutation prevention, we conclude that hMTH1 protects young mice against HFD by reducing genome instability during the early period of rapid growth and maximal gene expression. hMTH1 protection is redundant in the largely non‐growing, differentiated tissues of adult mice. In hMTH1‐Tg mice, expression of a less heavily mutated genome throughout life provides a plausible explanation for their extended longevity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
190. Evaluation of the risks for animal health related to the presence of hydroxymethylfurfural (HMF) in feed for honey bees.
- Author
-
Bodin, Laurent, del Mazo, Jesús, Grasl‐Kraupp, Bettina, Hogstrand, Christer, Leblanc, Jean‐Charles, Bignami, Margherita, Hoogenboom, Laurentius, Nebbia, Carlo Stefano, Nielsen, Elsa, Ntzani, Evangelia, Petersen, Annette, Schrenk, Dieter, Vleminckx, Christiane, Wallace, Heather, Focks, Andreas, Gregorc, Ales, Metzler, Manfred, Sgolastra, Fabio, Tosi, Simone, and Horvath, Zsuzsanna
- Subjects
- *
HONEYBEES , *ANIMAL health , *BEE products , *HYDROXYMETHYLFURFURAL , *BEE pollen , *RISK assessment , *BEES - Abstract
The European Commission has asked the EFSA to evaluate the risk for animal health related to the presence of hydroxymethylfurfural (HMF) in honey bee feed. HMF is a degradation product of particular sugars and can be present in bee feed. HMF is of low acute toxicity in bees but causes increased mortality upon chronic exposure. A benchmark dose lower limit 10% (BMDL10) of 1.16 μg HMF per bee per day has been calculated from mortalities observed in a 20‐day study and established as a Reference Point covering also mortality in larvae, drones and queens for which no or insufficient toxicity data were available. Winter bees have a much longer lifespan than summer bees and HMF shows clear time reinforced toxicity (TRT) characteristics. Therefore, additional Reference Point intervals of 0.21–3.1, 0.091–1.1 and 0.019–0.35 µg HMF/bee per day were calculated based on extrapolation to exposure durations of 50, 90 and 180 days, respectively. A total of 219 analytical data of HMF concentrations in bee feed from EU Member States and 88 from Industry were available. Exposure estimates of worker bees and larvae ranged between 0.1 and 0.48, and between 0.1 and 0.51 μg HMF/per day, respectively. They were well below the BMDL10 of 1.16 μg HMF/bee per day, and thus, no concern was identified. However, when accounting for TRT, the probability that exposures were below established reference point intervals was assessed to be extremely unlikely to almost certain depending on exposure duration. A concern for bee health was identified when bees are exposed to HMF contaminated bee feed for several months. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
191. Risk assessment of chlorinated paraffins in feed and food
- Author
-
EFSA Panel on Contaminants in the Food Chain (CONTAM), Dieter Schrenk, Marguerita Bignami, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Bettina Grasl‐Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean‐Charles Leblanc, Carlo Stefano Nebbia, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Beat Brüschweiler, Pim Leonards, Martin Rose, Marco Binaglia, Zsuzsanna Horváth, Luisa Ramos Bordajandi, Elsa Nielsen, European Commission, Schrenk, Dieter [0000-0002-7717-5533], Bodin, Laurent [0000-0001-5671-3139], Del Mazo, Jesús [0000-0003-3269-3895], Grasl-Kraupp, Bettina [0000-0003-4889-6531], Hogstrand, Christer [0000-0001-7545-6975], Hoogenboom, Laurentius (Ron) [0000-0002-8913-5328], Leblanc, Jean-Charles [0000-0003-2872-3414], Ntzani, Evangelia [0000-0003-3712-4181], Sand, Salomon [0000-0002-3360-0534], Schwerdtle, Tanja [0000-0002-4873-7488], Vleminckx, Christiane [0000-0002-9928-1601], Leonards, Pim [0000-0002-3052-8848], Nielsen, Elsa [0000-0002-6874-2575], Bignami, Margherita [0000-0002-1525-6864], Schrenk, Dieter, Bodin, Laurent, Del Mazo, Jesús, Grasl-Kraupp, Bettina, Hogstrand, Christer, Hoogenboom, Laurentius (Ron), Leblanc, Jean-Charles, Ntzani, Evangelia, Sand, Salomon, Schwerdtle, Tanja, Vleminckx, Christiane, Leonards, Pim, Nielsen, Elsa, and Bignami, Margherita
- Subjects
Novel Foods & Agrochains ,Physiology ,Plant Science ,010501 environmental sciences ,Novel Foods & Agroketens ,01 natural sciences ,0403 veterinary science ,Chlorinated paraffins ,Male rats ,Medicine ,LCCP ,TX341-641 ,BU Toxicology, Novel Foods & Agrochains ,ResearchInstitutes_Networks_Beacons/MERI ,Risk assessment ,Dietary exposure ,Incidence (epidemiology) ,BU Toxicology ,feed ,risk assessment ,04 agricultural and veterinary sciences ,Manchester Environmental Research Institute ,BU Toxicologie, Novel Foods & Agroketens ,Feed ,Toxicity ,SCCP ,040301 veterinary sciences ,BU Toxicologie ,Veterinary (miscellaneous) ,TP1-1185 ,chlorinated paraffins ,Microbiology ,SDG 3 - Good Health and Well-being ,0105 earth and related environmental sciences ,Exposure assessment ,VLAG ,business.industry ,Nutrition. Foods and food supply ,Chemical technology ,food ,Scientific Opinion ,Food ,Animal Science and Zoology ,Parasitology ,MCCP ,business ,Target organ ,Food Science - Abstract
220 p.-4 fig.-37 tab.-15 fig. compl.-16 tab. compl.-2 tab. append., The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of chlorinated paraffins in feed and food. The data for experimental animals were reviewed and the CONTAM Panel identified the liver, kidney and thyroid as the target organs for the SCCP and MCCP mixtures tested in repeated dose toxicity studies. Decreased pup survival and subcutaneous haematoma/haemorrhage were also identified as critical effects for an MCCP mixture. For the LCCP mixtures tested, the liver was identified as the target organ. The Panel selected as reference points a BMDL10 of 2.3 mg/kg bw per day for increased incidence of nephritis in male rats, and of 36 mg/kg bw per day for increased relative kidney weights in male and female rats for SCCPs and MCCPs, respectively. For LCCPs, a reference point relevant for humans could not be identified. Due to the limitations in the toxicokinetic and toxicological database, the Panel concluded that derivation of a health-based guidance value was not appropriate. Only limited data on the occurrence of SCCPs and MCCPs in some fish species were submitted to EFSA. No data were submitted for LCCPs. Thus, a robust exposure assessment and consequently a complete risk characterisation could not be performed. A preliminary risk characterisation based only on the consumption of fish was performed, and the calculated margins of exposure suggested no health concern for this limited scenario. The Panel noted that dietary exposure will be higher due to the contribution of CPs from other foods. The Panel was not able to identify reference points for farm animals, horses and companion animals. No occurrence data for feed were submitted to EFSA.Therefore, no risk characterisation could be performed for any of these animal species., The Panel wishes to thank the hearing expert: Kerstin Krätschmer and EFSA staff member: Kelly Niermans for the support provided to this scientific output. The CONTAM Panel acknowledges all European competent institutions and other stakeholders that provided occurrence data in food and human milk and data on the toxicity of CPs, and supported the data collection for the Comprehensive European Food Consumption Database.
- Published
- 2020
192. Risk assessment of ochratoxin A in food
- Author
-
EFSA Panel on Contaminants in the Food Chain (CONTAM), Dieter Schrenk, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Bettina Grasl‐Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean‐Charles Leblanc, Carlo Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Jan Alexander, Chiara Dall'Asta, Angela Mally, Manfred Metzler, Marco Binaglia, Zsuzsanna Horváth, Hans Steinkellner, Margherita Bignami, Schrenk, Dieter [0000-0002-7717-5533], Bodin, Laurent [0000-0001-5671-3139], Del Mazo, Jesús [0000-0003-3269-3895], Grasl-Kraupp, Bettina [0000-0003-4889-6531], Hogstrand, Christer [0000-0001-7545-6975], Hoogenboom, Laurentius (Ron) [0000-0002-8913-5328], Leblanc, Jean-Charles [0000-0003-2872-3414], Nielsen, Elsa [0000-0002-6874-2575], Ntzani, Evangelia [0000-0003-3712-4181], Sand, Salomon [0000-0002-3360-0534], Schwerdtle, Tanja [0000-0002-4873-7488], Vleminckx, Christiane [0000-0002-9928-1601], Dall'Asta, Chiara [http://orcid.org/0000-0003-0716-8394], Mally, Angela [https://orcid.org/0000-0002-5013-5080], Bignami, Margherita [0000-0002-1525-6864], Schrenk, Dieter, Bodin, Laurent, Del Mazo, Jesús, Grasl-Kraupp, Bettina, Hogstrand, Christer, Hoogenboom, Laurentius (Ron), Leblanc, Jean-Charles, Nielsen, Elsa, Ntzani, Evangelia, Sand, Salomon, Schwerdtle, Tanja, Vleminckx, Christiane, Dall'Asta, Chiara, Mally, Angela, and Bignami, Margherita
- Subjects
Ochratoxin A ,Hazard characterisation ,Percentile ,Novel Foods & Agrochains ,BU Toxicologie ,040301 veterinary sciences ,Veterinary (miscellaneous) ,Physiology ,TP1-1185 ,Plant Science ,010501 environmental sciences ,Breast milk ,Novel Foods & Agroketens ,medicine.disease_cause ,01 natural sciences ,Microbiology ,0403 veterinary science ,chemistry.chemical_compound ,Margin of exposure approach ,risk characterisation ,Risk characterisation ,margin of exposure approach ,Medicine ,TX341-641 ,Dietary exposure assessment ,BU Toxicology, Novel Foods & Agrochains ,hazard characterisation ,Ochratoxin ,Carcinogen ,VLAG ,0105 earth and related environmental sciences ,Kidney ,Nutrition. Foods and food supply ,business.industry ,Chemical technology ,BU Toxicology ,dietary exposure assessment ,04 agricultural and veterinary sciences ,medicine.anatomical_structure ,BU Toxicologie, Novel Foods & Agroketens ,chemistry ,Animal Science and Zoology ,Parasitology ,business ,Risk assessment ,Genotoxicity ,Food Science - Abstract
150 p.-15 fig.-37 tab., The European Commission asked EFSA to update their 2006 opinion on ochratoxin A (OTA) in food. OTA is produced by fungi of the genus Aspergillus and Penicillium and found as a contaminant in various foods. OTA causes kidney toxicity in different animal species and kidney tumours in rodents. OTA is genotoxic both in vitro and in vivo; however, the mechanisms of genotoxicity are unclear. Direct and indirect genotoxic and non-genotoxic modes of action might each contribute to tumour formation. Since recent studies have raised uncertainty regarding the mode of action for kidney carcinogenicity, it is inappropriate to establish a health-based guidance value (HBGV) and a margin of exposure (MOE) approach was applied. For the characterisation of non-neoplastic effects, a BMDL10 of 4.73 lg/kg body weight (bw) per day was calculated from kidney lesions observed in pigs. For characterisation of neoplastic effects, a BMDL10 of 14.5 lg/kg bw per day was calculated from kidney tumours seen in rats. The estimation of chronic dietary exposure resulted in mean and 95th percentile levels ranging from 0.6 to 17.8 and from 2.4 to 51.7 ng/kg bw per day, respectively. Median OTA exposures in breastfed infants ranged from 1.7 to 2.6 ng/kg bw per day, 95th percentile exposures from 5.6 to 8.5 ng/kg bw per day in average/high breast milk consuming infants, respectively. Comparison of exposures with the BMDL10 based on the non-neoplastic endpoint resulted in MOEs of more than 200 in most consumer groups, indicating a low health concern with the exception of MOEs for high consumers in the younger age groups, indicating a possible health concern. When compared with the BMDL10 based on the neoplastic endpoint, MOEs were lower than 10,000 for almost all exposure scenarios, including breastfed infants. This would indicate a possible health concern if genotoxicity is direct. Uncertainty in this assessment is high and risk may be overestimated.
- Published
- 2020
193. Risk assessment of glycoalkaloids in feed and food, in particular in potatoes and potato-derived products
- Author
-
EFSA Panel on Contaminants in the Food Chain (CONTAM), Dieter Schrenk, Margherita Bignami, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean‐Charles Leblanc, Carlo Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Leon Brimer, Bruce Cottrill, Birgit Dusemund, Patrick Mulder, Günter Vollmer, Marco Binaglia, Luisa Ramos Bordajandi, Francesca Riolo, Ruth Roldán‐Torres, Bettina Grasl‐Kraupp, European Commission, Schrenk, Dieter, Bignami, Margherita, Bodin, Laurent, Del Mazo, Jesús, Hogstrand, Christer, Hoogenboom, Laurentius (Ron), Leblanc, Jean-Charles, Nielsen, Elsa, Ntzani, Evangelia, Petersen, Annette, Sand, Salomon, Schwerdtle, Tanja, Vleminckx, Christiane, Grasl-Kraupp, Bettina, Schrenk, Dieter [0000-0002-7717-5533], Bignami, Margherita [0000-0002-1525-6864], Bodin, Laurent [0000-0001-5671-3139], Del Mazo, Jesús [0000-0003-3269-3895], Hogstrand, Christer [0000-0001-7545-6975], Hoogenboom, Laurentius (Ron) [0000-0002-8913-5328], Leblanc, Jean-Charles [0000-0003-2872-3414], Nielsen, Elsa [0000-0002-6874-2575], Ntzani, Evangelia [0000-0003-3712-4181], Petersen, Annette [0000-0003-3996-2701], Sand, Salomon [0000-0002-3360-0534], Schwerdtle, Tanja [0000-0002-4873-7488], Vleminckx, Christiane [0000-0002-9928-1601], and Grasl-Kraupp, Bettina [0000-0003-4889-6531]
- Subjects
Chronic exposure ,Younger age ,margin of exposure (MOE) ,Novel Foods & Agrochains ,Solanine ,BU Toxicologie ,040301 veterinary sciences ,Veterinary (miscellaneous) ,BU Contaminanten & Toxines ,Plant Science ,TP1-1185 ,010501 environmental sciences ,Biology ,Novel Foods & Agroketens ,01 natural sciences ,Microbiology ,solanine ,0403 veterinary science ,Toxicology ,Health problems ,chemistry.chemical_compound ,BU Contaminants & Toxins ,SDG 3 - Good Health and Well-being ,TX341-641 ,BU Toxicology, Novel Foods & Agrochains ,Adverse effect ,0105 earth and related environmental sciences ,VLAG ,Nutrition. Foods and food supply ,Chemical technology ,food ,BU Toxicology ,feed ,food and beverages ,glycoalkaloids (GAs) ,04 agricultural and veterinary sciences ,chaconine ,Scientific Opinion ,chemistry ,BU Toxicologie, Novel Foods & Agroketens ,Acute exposure ,potato ,Animal Science and Zoology ,Parasitology ,Chaconine ,Risk assessment ,Food Science - Abstract
190 p.-8 fig.-47 tab.-7 appendix tab., The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of glycoalkaloids (GAs) in feed and food. This risk assessment covers edible parts of potato plants and other food plants containing GAs, in particular, tomato and aubergine. In humans, acute toxic effects of potato GAs (a-solanine and a-chaconine) include gastrointestinal symptoms such as nausea, vomiting and diarrhoea. For these effects, the CONTAM Panel identified a lowest-observed-adverse-effect level of 1 mg total potato GAs/kg body weight (bw) per day as a reference point for the risk characterisation following acute exposure. In humans, no evidence of health problems associated with repeated or long-term intake of GAs via potatoes has been identified. No reference point for chronic exposure could be identified from the experimental animal studies. Occurrence data were available only for a-solanine and a-chaconine, mostly for potatoes. The acute dietary exposure to potato GAs was estimated using a probabilistic approach and applying processing factors for food. Due to the limited data available, a margin of exposure (MOE) approach was applied. The MOEs for the younger age groups indicate a health concern for the food consumption surveys with the highest mean exposure, as well as for the P95 exposure in all surveys.For adult age groups, the MOEs indicate a health concern only for the food consumption surveys with the highest P95 exposures. For tomato and aubergine GAs, the risk to human health could not be characterised due to the lack of occurrence data and the limited toxicity data. For horses, farm and companion animals, no risk characterisation for potato GAs could be performed due to insufficient data on occurrence in feed and on potential adverse effects of GAs in these species.
- Published
- 2020
194. A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer
- Author
-
Bignami, Margherita [Istituto Superiore di Sanita, Rome (Italy)]
- Published
- 2017
- Full Text
- View/download PDF
195. Safety assessment of 2‐methyloxolane as a food extraction solvent.
- Author
-
Lambré, Claude, Barat Baviera, José Manuel, Bolognesi, Claudia, Chesson, Andrew, Cocconcelli, Pier Sandro, Crebelli, Riccardo, Gott, David Michael, Grob, Konrad, Lampi, Evgenia, Mengelers, Marcel, Mortensen, Alicja, Steffensen, Inger‐Lise, Tlustos, Christina, Van Loveren, Henk, Vernis, Laurence, Zorn, Holger, Bignami, Margherita, Fürst, Peter, Tard, Alexandra, and Van Haver, Ellen
- Subjects
- *
SOLVENT extraction , *FOOD additives , *COMMERCIAL products , *BODY weight , *SAFETY , *GENETIC toxicology - Abstract
The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of 2‐methyloxolane as an extraction solvent under the intended conditions of use and the maximum residue limits (MRLs) proposed by the applicant. 2‐Methyloxolane is intended to be used in processes currently applying hexane for oil and protein extraction from plant sources or for extraction of food additives. The proposed MRLs for the following uses are: (i) 1 mg/kg in fat, oil or butter; (ii) 10 mg/kg in defatted protein products, defatted flour and other defatted solid ingredients; (iii) 1 mg/kg in food category 13 (foods intended for particular nutritional uses as defined by Directive 2009/39/EC); and (iv) 1 mg/kg for the extraction of food additives. The Panel calculated the dietary exposure with the highest potential maximum (95th percentile) for toddlers as 0.32 mg/kg body weight (bw) per day. Based on the available toxicological data, the Panel concluded that 2‐methyloxolane was rapidly metabolised with a low bioaccumulation potential and does not raise a concern for genotoxicity. The Panel identified different no observed adverse effect levels (NOAELs) in a subchronic oral toxicity study in rats, an oral developmental toxicity study and an extended one‐generation reproductive toxicity study, and a TDI of 1 mg/kg bw per day for 2‐methyloxolane was derived based on the lowest identified NOAEL (100 mg/kg bw per day) for reproductive and developmental toxicity. This TDI was not exceeded in any of the population groups at the mean and 95th percentile exposure. The Panel concluded that the extraction solvent 2‐methyloxolane does not raise a safety concern when used according to the intended conditions and at the proposed MRLs in the extracted foods or food ingredients. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
196. Werner syndrome helicase activity is essential in maintaining fragile site stability.
- Author
-
Pirzio, Livia Maria, Pichierri, Pietro, Bignami, Margherita, and Franchitto, Annapaola
- Subjects
- *
WERNER'S syndrome , *DNA helicases , *DNA replication , *EXONUCLEASES , *ATAXIA telangiectasia , *CELLS , *CHROMOSOMES - Abstract
WRN is a member of the RecQ family of DNA helicases implicated in the resolution of DNA structures leading to the stall of replication forks. Fragile sites have been proposed to be DNA regions particularly sensitive to replicative stress. Here, we establish that WRN is a key regulator of fragile site stability. We demonstrate that in response to mild doses of aphidicolin, WRN is efficiently relocalized in nuclear foci in replicating cells and that WRN deficiency is associated with accumulation of gaps and breaks at common fragile sites even under unperturbed conditions. By expressing WRN isoforms impaired in either helicase or exonuclease activity in defective cells, we identified WRN helicase activity as the function required for maintaining the stability of fragile sites. Finally, we find that WRN stabilizes fragile sites acting in a common pathway with the ataxia telangiectasia and Rad3 related replication checkpoint. These findings provide the first evidence of a crucial role for a helicase in protecting cells against chromosome breakage at normally occurring replication fork stalling sites. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
197. Human mismatch repair, drug-induced DNA damage, and secondary cancer
- Author
-
Karran, Peter, Offman, Judith, and Bignami, Margherita
- Subjects
- *
DNA repair , *GENETIC mutation , *GASTROINTESTINAL system , *CANCER - Abstract
DNA mismatch repair (MMR) is an important replication error avoidance mechanism that prevents mutation. The association of defective MMR with familial and sporadic gastrointestinal and endometrial cancer has been acknowledged for some years. More recently, it has become apparent that MMR defects are common in acute myeloid leukaemia/myelodysplastic syndrome (AML/MDS) that follows successful chemotherapy for a primary malignancy. Therapy-related haematological malignancies are often associated with treatment with alkylating agents. Their frequency is increasing and they now account for at least 10% of all AML cases. There is also evidence for an association between MMR deficient AML/MDS and immunosuppressive treatment with thiopurine drugs. Here we review how MMR interacts with alkylating agent and thiopurine-induced DNA damage and suggest possible ways in which MMR defects may arise in therapy-related AML/MDS. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
- View/download PDF
198. Scientific opinion on the risks for animal and human health related to the presence of quinolizidine alkaloids in feed and food, in particular in lupins and lupin-derived products
- Author
-
EFSA Panel on Contaminants in the Food Chain (CONTAM), Dieter Schrenk, Laurent Bodin, James Kevin Chipman, Jesús del Mazo, Bettina Grasl‐Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Jean‐Charles Leblanc, Carlo Stefano Nebbia, Elsa Nielsen, Evangelia Ntzani, Annette Petersen, Salomon Sand, Tanja Schwerdtle, Christiane Vleminckx, Heather Wallace, Jan Alexander, Bruce Cottrill, Birgit Dusemund, Patrick Mulder, Davide Arcella, Katleen Baert, Claudia Cascio, Hans Steinkellner, Margherita Bignami, Schrenk, Dieter, Bodin, Laurent, Del Mazo, Jesús, Grasl-Kraupp, Bettina, Hogstrand, Christer, Hoogenboom, Laurentius (Ron), Leblanc, Jean-Charles, Nielsen, Elsa, Ntzani, Evangelia, Sand, Salomon, Schwerdtle, Tanja, Vleminckx, Christiane, Arcella, Davide, Cascio, Claudia, Bignami, Margherita, Schrenk, Dieter [0000-0002-7717-5533], Bodin, Laurent [0000-0001-5671-3139], Del Mazo, Jesús [0000-0003-3269-3895], Grasl-Kraupp, Bettina [0000-0003-4889-6531], Hogstrand, Christer [0000-0001-7545-6975], Hoogenboom, Laurentius (Ron) [0000-0002-8913-5328], Leblanc, Jean-Charles [0000-0003-2872-3414], Nielsen, Elsa [0000-0002-6874-2575], Ntzani, Evangelia [0000-0003-3712-4181], Sand, Salomon [0000-0002-3360-0534], Schwerdtle, Tanja [0000-0002-4873-7488], Vleminckx, Christiane [0000-0002-9928-1601], Arcella, Davide [https://orcid.org/0000-0003-3179-1426], Cascio, Claudia [0000-0002-3810-4134], and Bignami, Margherita [0000-0002-1525-6864]
- Subjects
margin of exposure (MOE) ,040301 veterinary sciences ,Veterinary (miscellaneous) ,BU Contaminanten & Toxines ,Plant Science ,TP1-1185 ,010501 environmental sciences ,01 natural sciences ,Microbiology ,0403 veterinary science ,Toxicology ,chemistry.chemical_compound ,Lupinus ,BU Contaminants & Toxins ,food ,SDG 3 - Good Health and Well-being ,quinolizidine alkaloid ,sparteine ,TX341-641 ,0105 earth and related environmental sciences ,VLAG ,Quinolizidine ,biology ,business.industry ,Nutrition. Foods and food supply ,Chemical technology ,feed ,lupanine ,Lupinus mutabilis ,04 agricultural and veterinary sciences ,biology.organism_classification ,Food safety ,food.food ,Lupinus luteus ,Lupinus angustifolius ,Scientific Opinion ,chemistry ,Lupin ,Animal Science and Zoology ,Parasitology ,Livestock ,business ,Risk assessment ,Food Science - Abstract
113 p.-8 fig.-32 tab., The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of quinolizidine alkaloids (QAs) in feed and food. This risk assessment is limited to QAs occurring in Lupinus species/varieties relevant for animal and human consumption in Europe (i.e. Lupinus albus L., Lupinus angustifolius L., Lupinus luteus L. and Lupinus mutabilis Sweet). Information on the toxicity of QAs in animals and humans is limited. Following acute exposure to sparteine (reference compound), anticholinergic effects and changes in cardiac electric conductivity are considered to be critical for human hazard characterisation. The CONTAM Panel used a margin of exposure (MOE) approach identifying a lowest single oral effective dose of 0.16 mg sparteine/kg body weight as reference point to characterise the risk following acute exposure. No reference point could be identified to characterise the risk of chronic exposure. Because of similar modes of action for QAs, the CONTAM Panel used a group approach assuming dose additivity. For food, the highest mean concentration of Total QAs (TotQAs) (i.e. the 6 most abundant QAs) was found in lupin seed samples classified as ‘Lupins (dry) and similar-’. Due to the limited data on occurrence and consumption, dietary exposure was calculated for some specific scenarios and no full human health risk characterisation was possible. The calculated margin of exposures (MOEs) may indicate a risk for some consumers. For example, when lupin seeds are consumed without a debittering step, or as debittered lupin seeds high in QA content and when ‘lupin-based meat imitates’ are consumed. For horses, companion and farm animals, other than salmonids, the available database on adverse effects was too limited to identify no-observed-adverse-effect levels and/or lowest-observed-adverse-effect levels and no risk characterisation was possible. For salmonids, the CONTAM Panel considers the risk for adverse effects to be low., The Panel wishes to thank the following for the support provided to this scientific output: Giovanna Boschin and Elena Rovesti. The Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output.
- Published
- 2019
199. Guidance on aneugenicity assessment.
- Author
-
More, Simon John, Bampidis, Vasileios, Bragard, Claude, Halldorsson, Thorhallur Ingi, Hernández-Jerez, Antonio F, Bennekou, Susanne Hougaard, Koutsoumanis, Kostas, Lambré, Claude, Machera, Kyriaki, Naegeli, Hanspeter, Nielsen, Søren Saxmose, Schlatter, Josef, Schrenk, Dieter, Turck, Dominique, Younes, Maged, Aquilina, Gabriele, Bignami, Margherita, Bolognesi, Claudia, Crebelli, Riccardo, and Gürtler, Rainer
- Subjects
- *
BIOTRANSFORMATION (Metabolism) , *BONE marrow , *NUCLEOLUS , *GENETIC mutation , *RISK assessment - Abstract
The EFSA Scientific Committee was asked to provide guidance on the most appropriate in vivo tests to follow up on positive in vitro results for aneugenicity, and on the approach to risk assessment for substances that are aneugenic but not clastogenic nor causing gene mutations. The Scientific Committee confirmed that the preferred approach is to perform an in vivo mammalian erythrocyte micronucleus test with a relevant route of administration. If this is positive, it demonstrates that the substance is aneugenic in vivo. A negative result with evidence that the bone marrow is exposed to the test substance supports a conclusion that aneugenic activity is not expressed in vivo. If there is no evidence of exposure to the bone marrow, a negative result is viewed as inconclusive and further studies are required. The liver micronucleus assay, even though not yet fully validated, can provide supporting information for substances that are aneugenic following metabolic activation. The gastrointestinal micronucleus test, conversely, to be further developed, may help to assess aneugenic potential at the initial site of contact for substances that are aneugenic in vitro without metabolic activation. Based on the evidence in relation to mechanisms of aneugenicity, the Scientific Committee concluded that, in principle, health-based guidance values can be established for substances that are aneugenic but not clastogenic nor causing gene mutations, provided that a comprehensive toxicological database is available. For situations in which the toxicological database is not sufficient to establish health-based guidance values, some approaches to risk assessment are proposed. The Scientific Committee recommends further development of the gastrointestinal micronucleus test, and research to improve the understanding of aneugenicity to support risk assessment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
200. Risks to human and animal health related to the presence of moniliformin in food and feed.
- Author
-
Knutsen, Helle Katrine, Alexander, Jan, Barregård, Lars, Bignami, Margherita, Brüschweiler, Beat, Ceccatelli, Sandra, Cottrill, Bruce, Dinovi, Michael, Grasl-Kraupp, Bettina, Hogstrand, Christer, Hoogenboom, Laurentius (Ron), Nebbia, Carlo Stefano, Oswald, Isabelle P., Petersen, Annette, Rose, Martin, Roudot, Alain-Claude, Schwerdtle, Tanja, Vleminckx, Christiane, Vollmer, Günter, and Wallace, Heather
- Subjects
- *
ANIMAL health , *MONILIFORMIN , *ANIMAL feeds , *MYCOTOXINS , *FUSARIUM - Abstract
Moniliformin (MON) is a mycotoxin with low molecular weight primarily produced by Fusarium fungi and occurring predominantly in cereal grains. Following a request of the European Commission, the CONTAM Panel assessed the risk of MON to human and animal health related to its presence in food and feed. The limited information available on toxicity and on toxicokinetics in experimental and farm animals indicated haematotoxicity and cardiotoxicity as major adverse health effects of MON. MON causes chromosome aberrations in vitro but no in vivo genotoxicity data and no carcinogenicity data were identified. Due to the limitations in the available toxicity data, human acute or chronic health-based guidance values (HBGV) could not be established. The margin of exposure (MOE) between the no-observed-adverse-effect level (NOAEL) of 6.0 mg/kg body weight (bw) for cardiotoxicity from a subacute study in rats and the acute upper bound (UB) dietary exposure estimates ranged between 4,000 and 73,000. The MOE between the lowest benchmark dose lower confidence limit (for a 5% response - BMDL05) of 0.20 mg MON/kg bw per day for haematological hazards from a 28-day study in pigs and the chronic dietary human exposure estimates ranged between 370 and 5,000,000 for chronic dietary exposures. These MOEs indicate a low risk for human health but were associated with high uncertainty. The toxicity data available for poultry, pigs, and mink indicated a low or even negligible risk for these animals from exposure to MON in feed at the estimated exposure levels under current feeding practices. Assuming similar or lower sensitivity as for pigs, the CONTAM Panel considered a low or even negligible risk for the other animal species for which no toxicity data suitable for hazard characterisation were identified. Additional toxicity studies are needed and depending on their outcome, the collection of more occurrence data on MON in food and feed is recommended to enable a comprehensive human risk assessment. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.