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2. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Author

Goodson, William H, Lowe, Leroy, Carpenter, David O, Gilbertson, Michael, Manaf Ali, Abdul, Lopez de Cerain Salsamendi, Adela, Lasfar, Ahmed, Carnero, Amancio, Azqueta, Amaya, Amedei, Amedeo, Charles, Amelia K, Collins, Andrew R, Ward, Andrew, Salzberg, Anna C, Colacci, Annamaria, Olsen, Ann-Karin, Berg, Arthur, Barclay, Barry J, Zhou, Binhua P, Blanco-Aparicio, Carmen, Baglole, Carolyn J, Dong, Chenfang, Mondello, Chiara, Hsu, Chia-Wen, Naus, Christian C, Yedjou, Clement, Curran, Colleen S, Laird, Dale W, Koch, Daniel C, Carlin, Danielle J, Felsher, Dean W, Roy, Debasish, Brown, Dustin G, Ratovitski, Edward, Ryan, Elizabeth P, Corsini, Emanuela, Rojas, Emilio, Moon, Eun-Yi, Laconi, Ezio, Marongiu, Fabio, Al-Mulla, Fahd, Chiaradonna, Ferdinando, Darroudi, Firouz, Martin, Francis L, Van Schooten, Frederik J, Goldberg, Gary S, Wagemaker, Gerard, Nangami, Gladys N, Calaf, Gloria M, Williams, Graeme, Wolf, Gregory T, Koppen, Gudrun, Brunborg, Gunnar, Lyerly, H Kim, Krishnan, Harini, Ab Hamid, Hasiah, Yasaei, Hemad, Sone, Hideko, Kondoh, Hiroshi, Salem, Hosni K, Hsu, Hsue-Yin, Park, Hyun Ho, Koturbash, Igor, Miousse, Isabelle R, Scovassi, A Ivana, Klaunig, James E, Vondráček, Jan, Raju, Jayadev, Roman, Jesse, Wise, John Pierce, Whitfield, Jonathan R, Woodrick, Jordan, Christopher, Joseph A, Ochieng, Josiah, Martinez-Leal, Juan Fernando, Weisz, Judith, Kravchenko, Julia, Sun, Jun, Prudhomme, Kalan R, Narayanan, Kannan Badri, Cohen-Solal, Karine A, Moorwood, Kim, Gonzalez, Laetitia, Soucek, Laura, Jian, Le, D'Abronzo, Leandro S, Lin, Liang-Tzung, Li, Lin, Gulliver, Linda, McCawley, Lisa J, Memeo, Lorenzo, Vermeulen, Louis, Leyns, Luc, Zhang, Luoping, Valverde, Mahara, Khatami, Mahin, Romano, Maria Fiammetta, Chapellier, Marion, Williams, Marc A, and Wade, Mark

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, 2.2 Factors relating to the physical environment, Animals, Carcinogenesis, Carcinogens, Environmental, Environmental Exposure, Hazardous Substances, Humans, Neoplasms, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Published
2015

10. Causes of genome instability: the effect of low dose chemical exposures in modern society

Author

Langie, Sabine A.S., Koppen, Gudrun, Desaulniers, Daniel, Al-Mulla, Fahd, Al-Temaimi, Rabeah, Amedei, Amedeo, Azqueta, Amaya, Bisson, William H., Brown, Dustin, Brunborg, Gunnar, Charles, Amelia K., Chen, Tao, Colacci, Annamaria, Darroudi, Firouz, Forte, Stefano, Gonzalez, Laetitia, Hamid, Roslida A., Knudsen, Lisbeth E., Leyns, Luc, Lopez de Cerain Salsamendi, Adela, Memeo, Lorenzo, Mondello, Chiara, Mothersill, Carmel, Olsen, Ann-Karin, Pavanello, Sofia, Raju, Jayadev, Rojas, Emilio, Roy, Rabindra, Ryan, Elizabeth, Ostrosky-Wegman, Patricia, Salem, Hosni K., Scovassi, Ivana, Singh, Neetu, Vaccari, Monica, Van Schooten, Frederik J., Valverde, Mahara, Woodrick, Jordan, Zhang, Luoping, van Larebeke, Nik, Kirsch-Volders, Micheline, and Collins, Andrew R.

Published
2015
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11. International study of factors affecting human chromosome translocations

Author

Sigurdson, Alice J., Ha, Mina, Hauptmann, Michael, Bhatti, Parveen, Sram, Radim J., Beskid, Olena, Tawn, E. Janet, Whitehouse, Caroline A., Lindholm, Carita, Nakano, Mimako, Kodama, Yoshiaki, Nakamura, Nori, Vorobtsova, Irena, Oestreicher, Ursula, Stephan, Günther, Yong, Lee C., Bauchinger, Manfred, Schmid, Ernst, Chung, Hai Won, Darroudi, Firouz, Roy, Laurence, Voisin, Phillipe, Barquinero, Joan F., Livingston, Gordon, Blakey, David, Hayata, Isamu, Zhang, Wei, Wang, Chunyan, Bennett, L. Michelle, Littlefield, L. Gayle, Edwards, Alan A., Kleinerman, Ruth A., and Tucker, James D.

Published
2008
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13. How to reduce false positive results when undertaking in vitro genotoxicity testing and thus avoid unnecessary follow-up animal tests: Report of an ECVAM Workshop

Author

Kirkland, David, Pfuhler, Stefan, Tweats, David, Aardema, Marilyn, Corvi, Raffaella, Darroudi, Firouz, Elhajouji, Azeddine, Glatt, Hansruedi, Hastwell, Paul, Hayashi, Makoto, Kasper, Peter, Kirchner, Stephan, Lynch, Anthony, Marzin, Daniel, Maurici, Daniela, Meunier, Jean-Roc, Müller, Lutz, Nohynek, Gerhard, Parry, James, Parry, Elizabeth, Thybaud, Veronique, Tice, Ray, van Benthem, Jan, Vanparys, Philippe, and White, Paul

Published
2007
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15. Contributors

Author

Al-Taher, Fadwa, primary, Anelich, Lucia E., additional, Appaiah, Kalapanda M., additional, Ariosti, Alejandro, additional, Baines, Janis, additional, Barbosa-Canovas, Gustavo V., additional, Bermúdez-Aguirre, Daniela, additional, Boisrobert, Christine E., additional, Bouwmeester, Hans, additional, Bovell-Benjamin, Adelia C., additional, Brent, Paul, additional, Bricher, Julie Larson, additional, Bromfield, Elaine, additional, Busta, Frank F., additional, Cole, Martin, additional, Coleman, Pamela L., additional, Darroudi, Firouz, additional, Dubois, Thibaut, additional, Ehrlich, Veronika, additional, Fontana, Anthony J., additional, Fortin, Neal D., additional, Hambridge, Tracy, additional, Hanekamp, Jaap C., additional, Hegarty, Vincent, additional, Isengard, Heinz-Dieter, additional, Jackson, Lauren S., additional, Jansson, Edward, additional, Kampers, Frans W.H., additional, Keener, Larry, additional, Kim, Ji Yeon, additional, Knasmüller, Siegfried, additional, Kopper, Gisela, additional, Kwakman, Jan H.J.M., additional, Kwon, Oran, additional, Lelieveld, Huub L.M., additional, López-García, Rebeca, additional, Mersch-Sundermann, Volker, additional, Miles, David, additional, Moraru, Carmen, additional, Oh, Sangsuk, additional, Porter, William R., additional, Poto, Margherita, additional, Prakash, V., additional, Richardson, Keith C., additional, Rizvi, Syed S.H., additional, Sattigeri, Vijay D., additional, Schwitters, Bert, additional, Sohn, Mun-Gi, additional, Stanley, Glenn, additional, Stewart, Cynthia M., additional, Sun, Juanjuan, additional, Surak, John G., additional, Szabo, Elizabeth A., additional, van Boekel, Martinus AJS (Tiny), additional, van der Meulen, Bernd, additional, Varadaraj, Mandyam C., additional, Vasilyev, Yuriy, additional, and Wuillot, Axelle, additional

Published
2010
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23. List of contributors

Author

Al-Taher, Fadwa, Andersen, Veslemøy, Ariosti, Alejandro, Arundell, Elisabeth J., Baicu, Adina Alexandra, Barbosa-Cánovas, Gustavo V., Bermúdez-Aguirre, Daniela, Bilgin, Fehmi Kerem, Bourke, Paula, Bouwmeester, Hans, Bovell-Benjamin, Adelia C., Bricher, Julie Larson, Busta, Frank F., Candoğan, Kezban, Card, Melissa M., Cheng, Yifan, Cole, M.B., Coleman, Pamela L., Darroudi, Firouz, Dasgupta, Debdeep, De Zoysa, H.K.S., Din, Ahmad, Farrell, Hazel, Fontana, Anthony J., Fortin, Neal D., Gonçalves Franco, Beatriz, Gorris, L.G.M., Hanekamp, Jaap C., Henry-Unaeze, Helen Nonye, Imlay, Alison, Isengard, Heinz-Dieter, Jackson, Lauren S., Jeong, Sewon, Jones, Katy A., Kampers, Frans W.H., Keener, Larry, Kim, Ji Yeon, King, Thea, Koutchma, Tatiana, Kwon, Oran, Lederman, Joe, Lelieveld, Huub, López-García, Rebeca, Mahmudova, Alida, Maister, Bernard, Moraru, Carmen I., Oh, Sangsuk, Poto, Margherita Paola, Prakash, Jamuna, Rizvi, Syed S.H., Sattigeri, V.D., Schwitters, Bert, Shadbolt, Craig, Shi, Xian-Ming, Shin, Ga Young, Sohn, Mungi, Stewart, Cynthia M., Sun, Juanjuan, Szabo, Elizabeth A., Szpylka, John, Tang, John Y.H., Taylor, Matthew D., The International Commission on Microbiological Specifications for Foods, Türkoğlu, Halide Gökçe, Urazbaeva, Altinay, van Boekel, M.A.J.S., van der Meulen, Bernd, Varadaraj, Mandyam C., Vasiliev, Yuriy, Waisundara, Viduranga Y., and Yun LI, Odel

Published
2022
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24. Potent cytotoxic effects of Calomeria amaranthoides on ovarian cancers

Author

van Haard Paul MM, Smit Nico PM, Weerheim Arij M, Duke Colin C, van Haaften Caroline, Darroudi Firouz, and Trimbos Baptist JMZ

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Ovarian cancer remains the leading cause of death from gynaecological malignancy. More than 60% of the patients are presenting the disease in stage III or IV. In spite of combination of chemotherapy and surgery the prognosis stays poor for therapy regimen. Methods The leaves of a plant endemic to Australia, Calomeria amaranthoides, were extracted and then fractionated by column chromatography. In vitro cytotoxicity tests were performed with fractions of the plant extract and later with an isolated compound on ovarian cancer cell lines, as well as normal fibroblasts at concentrations of 1-100 μg/mL (crude extract) and 1-10 μg/mL (compound). Cytotoxicity was measured after 24, 48 and 72 hours by using a non-fluorescent substrate, Alamar blue. In vivo cytotoxicity was tested on ascites, developed in the abdomen of nude mice after inoculation with human OVCAR3 cells intraperitoneally. The rate of change in abdomen size for the mice was determined by linear regression and statistically evaluated for significance by the unpaired t test. Results Two compounds were isolated by chromatographic fractionation and identified by 1H-NMR, 13C-NMR and mass spectrometry analyses, EPD, an α-methylene sesquiterpene lactone of the eremophilanolide subtype, and EPA, an α-methylene carboxylic acid. Cytotoxicity of EPD for normal fibroblasts at all time points IC50 was greater than 10 μg/mL, whereas, for OVCAR3 cells at 48 hours IC50 was 5.3 μg/mL (95% confidence interval 4.3 to 6.5 μg/mL). Both, the crude plant extract as well as EPD killed the cancer cells at a final concentration of 10 μg/mL and 5 μg/mL respectively, while in normal cells only 20% cell killing effect was observed. EPA had no cytotoxic effects. Changes in abdomen size for control versus Cisplatin treated mice were significantly different, P = 0.023, as were control versus EPD treated mice, P = 0.025, whereas, EPD versus Cisplatin treated mice were not significantly different, P = 0.13. Conclusions For the first time both crude plant extract from Calomeria amaranthoides and EPD have been shown to have potent anti-cancer effects against ovarian cancer.

Published
2011
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26. Assessing the applicability of FISH-based prematurely condensed dicentric chromosome assay in triage biodosimetry

Author

Darroudi, Firouz

Abstract

The dicentric chromosome assay (DCA) has been regarded as the gold standard of radiation biodosimetry. The assay, however, requires a 2-d peripheral blood lymphocyte culture before starting metaphase chromosome analyses to estimate biological doses. Other biological assays also have drawbacks with respect to the time needed to obtain dose estimates for rapid decision on the correct line of medical treatment. Therefore, alternative technologies that suit requirements for triage biodosimetry are needed. Radiation-induced DNA double strand breaks in G0 lymphocytes can be detected as interphase chromosome aberrations by the cell fusion-mediated premature chromosome condensation (PCC) method. The method, in combination with fluorescence in situ hybridization (FISH) techniques, has been proposed in early studies as a powerful tool for obtaining biological dose estimates without 2-d lymphocyte culture procedures. The present work assesses the applicability of FISH-based PCC techniques using pan-centromeric and telomeric peptide nucleic acid (PNA) probes in triage mode biodosimetry and demonstrates that an improved rapid procedure of the prematurely condensed dicentric chromosome (PCDC) assay has the potential for evaluating exposed radiation doses in as short as 6 h after the collection of peripheral blood specimens.

Published
2015

27. RENEB biodosimetry intercomparison analyzing translocations by FISH

Author

Barquinero, Joan Francesc, Beinke, Christina, Borras, Mireia, Buraczewska, Iwona, Darroudi, Firouz, Gregoire, Eric, Hristova, Rositsa, Kulka, Ulrike, Lindholm, Carita, Moreno, Mercedes, Moquet, Jayne, Oestreicher, Ursula, Prieto, M. Jesus, Pujol, Monica, Ricoul, Michelle, Sabatier, Laure, Sommer, Sylwester, Sun, Mingzhu, Wojcik, Andrzej, Leonardo Barrios, Universitat Autònoma de Barcelona (UAB), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Hospital General Universitario 'Gregorio Marañón' [Madrid], Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Public Health England [London], and Seventh Framework Programme, FP7 295513

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; Purpose In the framework of RENEB, several biodosimetry exercises were conducted analyzing different endpoints. Among them, the analysis of translocations is considered the most useful method for retrospective biodosimetry due to the relative stability of their frequency with post irradiation time. The aim of this study was to harmonize the accuracy of translocation-based biodosimetry within the RENEB consortium. Materials and methods An initial telescoring exercise analyzing FISH metaphase images was done to harmonize chromosome aberration descriptions. Then two blind intercomparison exercises (IE) were performed, by sending irradiated blood samples to each partner. Samples were cultured and stained by each partner using their standard protocol and translocation frequency was used to produce dose estimates. Results The coefficient of variation in the 1st IE (CV = 0.34) was higher than in the 2nd IE (CV = 0.16 and 0.23 in the two samples analyzed), for the genomic frequency of total translocations. Z-score analysis revealed that eight out of 10 and 17 out of 20 dose estimates were satisfactory in the 1st and 2nd IE, respectively. Conclusions The results obtained indicate that, despite the problems identified in few partners, which can be corrected, the RENEB consortium is able to carry out retrospective biodosimetry analyzing the frequency of translocations by FISH. © 2016 The Author(s). Published by Informa UK Limited, trading as Taylor and Francis Group.

Published
2017

28. Dose assessment intercomparisons within the RENEB network using G(0)-lymphocyte prematurely condensed chromosomes (PCC assay)

Author

Terzoudi, Georgia I, Pantelias, Gabriel, Darroudi, Firouz, Barszczewska, Katarzyna, Buraczewska, Iwona, Depuydt, Julie, Georgieva, Dimka, Hadjidekova, Valeria, Hatzi, Vasiliki I, Karachristou, Ioanna, Karakosta, Maria, Meschini, Roberta, M’Kacher, Radhia, Montoro, Alegria, Palitti, Fabrizio, Pantelias, Antonio, Pepe, Gaetano, Ricoul, Michelle, Sabatier, Laure, Sebastià, Natividad, Sommer, Sylwester, Vral, Anne, Zafiropoulos, Demetre, and Wojcik, Andrzej

Subjects
cell fusion, EXCHANGES, centromere/telomere PNA FISH, Biology and Life Sciences, Biodosimetry, IRRADIATED HUMAN-LYMPHOCYTES, PCC assay, PROBES, PERIPHERAL-BLOOD LYMPHOCYTES, FISH, TRIAGE BIODOSIMETRY, premature chromosome condensation, RADIATION, COMBINATION, BIOLOGICAL DOSIMETRY, FRAGMENTS
Abstract

Purpose: Dose assessment intercomparisons within the RENEB network were performed for triage biodosimetry analyzing G(0)-lymphocyte PCC for harmonization, standardization and optimization of the PCC assay. Materials and methods: Comparative analysis among different partners for dose assessment included shipment of PCC-slides and captured images to construct dose-response curves for up to 6 Gy gamma-rays. Accident simulation exercises were performed to assess the suitability of the PCC assay by detecting speed of analysis and minimum number of cells required for categorization of potentially exposed individuals. Results: Calibration data based on Giemsa-stained fragments in excess of 46 PCC were obtained by different partners using galleries of PCC images for each dose-point. Mean values derived from all scores yielded a linear dose-response with approximately 4 excess-fragments/cell/Gy. To unify scoring criteria, exercises were carried out using coded PCC-slides and/or coded irradiated blood samples. Analysis of samples received 24h post-exposure was successfully performed using Giemsa staining (1 excess-fragment/cell/Gy) or centromere/telomere FISH-staining for dicentrics. Conclusions: Dose assessments by RENEB partners using appropriate calibration curves were mostly in good agreement. The PCC assay is quick and reliable for whole- or partial-body triage biodosimetry by scoring excess-fragments or dicentrics in G(0)-lymphocytes. Particularly, analysis of Giemsa-stained excess PCC-fragments is simple, inexpensive and its automation could increase throughput and scoring objectivity of the PCC assay.

Published
2017

29. RENEB intercomparison exercises analyzing micronuclei (Cytokinesis-block Micronucleus Assay)

Author

Depuydt, Julie, Baeyens, Ans, Barnard, Stephen, Beinke, Christina, Benedek, Anett, Beukes, Philip, Buraczewska, Iwona, Darroudi, Firouz, De Sanctis, Stefania, Domingue, Inmaculada, Gil, Octavia Monteiro, Hadjidekova, Valeria, Kis, Eniko, Kulka, Ulrike, Lista, Florigio, Lumniczky, Katalin, M'kacher, Radhia, Moquet, Jayne, Obreja, Doina, Oestreicher, Ursula, Pajic, Jelena, Pastor, Nuria, Popova, Ljubomira, Regalbuto, Elisa, Ricoul, Michelle, Sabatier, Laure, Slabbert, Jacobus, Sommer, Sylwester, Testa, Antonella, Thierens, Hubert, Wojcik, Andrzej, Vral, Anne, Depuydt, Julie, Baeyens, Ans, Barnard, Stephen, Beinke, Christina, Benedek, Anett, Beukes, Philip, Buraczewska, Iwona, Darroudi, Firouz, De Sanctis, Stefania, Domingue, Inmaculada, Gil, Octavia Monteiro, Hadjidekova, Valeria, Kis, Eniko, Kulka, Ulrike, Lista, Florigio, Lumniczky, Katalin, M'kacher, Radhia, Moquet, Jayne, Obreja, Doina, Oestreicher, Ursula, Pajic, Jelena, Pastor, Nuria, Popova, Ljubomira, Regalbuto, Elisa, Ricoul, Michelle, Sabatier, Laure, Slabbert, Jacobus, Sommer, Sylwester, Testa, Antonella, Thierens, Hubert, Wojcik, Andrzej, and Vral, Anne

Abstract

Purpose: In the framework of the 'Realizing the European Network of Biodosimetry' (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, and four non-RENEB labs were added in the second one. Materials and methods: Irradiated blood samples were shipped to participating labs, whose task was to culture these samples and provide a blind dose estimate. Micronucleus analysis was performed by automated, semi-automated and manual procedures. Results: The dose estimates provided by network laboratories were in good agreement with true administered doses. The most accurate estimates were reported for low dose points (<= 0.94 Gy). For higher dose points (>= 2.7 Gy) a larger variation in estimates was observed, though in the second exercise the number of acceptable estimates increased satisfactorily. Higher accuracy was achieved with the semi-automated method. Conclusion: The results of the two exercises performed by our network demonstrate that the micronucleus assay is a useful tool for large-scale radiation emergencies, and can be successfully implemented within a large network of laboratories.

Published
2017
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30. RENEB biodosimetry intercomparison analyzing translocations by FISH

Author

Francesc Barquinero, Joan, Beinke, Christina, Borras, Mireia, Buraczewska, Iwona, Darroudi, Firouz, Gregoire, Eric, Hristova, Rositsa, Kulka, Ulrike, Lindholm, Carita, Moreno, Mercedes, Moquet, Jayne, Oestreicher, Ursula, Jesus Prieto, M., Pujol, Monica, Ricoul, Michelle, Sabatier, Laure, Sommer, Sylwester, Sun, Mingzhu, Wojcik, Andrzej, Barrios, Leonardo, Francesc Barquinero, Joan, Beinke, Christina, Borras, Mireia, Buraczewska, Iwona, Darroudi, Firouz, Gregoire, Eric, Hristova, Rositsa, Kulka, Ulrike, Lindholm, Carita, Moreno, Mercedes, Moquet, Jayne, Oestreicher, Ursula, Jesus Prieto, M., Pujol, Monica, Ricoul, Michelle, Sabatier, Laure, Sommer, Sylwester, Sun, Mingzhu, Wojcik, Andrzej, and Barrios, Leonardo

Abstract

Purpose: In the framework of RENEB, several biodosimetry exercises were conducted analyzing different endpoints. Among them, the analysis of translocations is considered the most useful method for retrospective biodosimetry due to the relative stability of their frequency with post irradiation time. The aim of this study was to harmonize the accuracy of translocation-based biodosimetry within the RENEB consortium. Materials and methods: An initial telescoring exercise analyzing FISH metaphase images was done to harmonize chromosome aberration descriptions. Then two blind intercomparison exercises (IE) were performed, by sending irradiated blood samples to each partner. Samples were cultured and stained by each partner using their standard protocol and translocation frequency was used to produce dose estimates. Results: The coefficient of variation in the 1st IE (CV = 0.34) was higher than in the 2nd IE (CV = 0.16 and 0.23 in the two samples analyzed), for the genomic frequency of total translocations. Z-score analysis revealed that eight out of 10 and 17 out of 20 dose estimates were satisfactory in the 1st and 2nd IE, respectively. Conclusions: The results obtained indicate that, despite the problems identified in few partners, which can be corrected, the RENEB consortium is able to carry out retrospective biodosimetry analyzing the frequency of translocations by FISH.

Published
2017
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31. Dose assessment intercomparisons within the RENEB network using G(0)-lymphocyte prematurely condensed chromosomes (PCC assay)

Author

Terzoudi, Georgia I., Pantelias, Gabriel, Darroudi, Firouz, Barszczewska, Katarzyna, Buraczewska, Iwona, Depuydt, Julie, Georgieva, Dimka, Hadjidekova, Valeria, Hatzi, Vasiliki I., Karachristou, Ioanna, Karakosta, Maria, Meschini, Roberta, M'Kacher, Radhia, Montoro, Alegria, Palitti, Fabrizio, Pantelias, Antonio, Pepe, Gaetano, Ricoul, Michelle, Sabatier, Laure, Sebastia, Natividad, Sommer, Sylwester, Vral, Anne, Zafiropoulos, Demetre, Wojcik, Andrzej, Terzoudi, Georgia I., Pantelias, Gabriel, Darroudi, Firouz, Barszczewska, Katarzyna, Buraczewska, Iwona, Depuydt, Julie, Georgieva, Dimka, Hadjidekova, Valeria, Hatzi, Vasiliki I., Karachristou, Ioanna, Karakosta, Maria, Meschini, Roberta, M'Kacher, Radhia, Montoro, Alegria, Palitti, Fabrizio, Pantelias, Antonio, Pepe, Gaetano, Ricoul, Michelle, Sabatier, Laure, Sebastia, Natividad, Sommer, Sylwester, Vral, Anne, Zafiropoulos, Demetre, and Wojcik, Andrzej

Abstract

Purpose: Dose assessment intercomparisons within the RENEB network were performed for triage biodosimetry analyzing G(0)-lymphocyte PCC for harmonization, standardization and optimization of the PCC assay. Materials and methods: Comparative analysis among different partners for dose assessment included shipment of PCC-slides and captured images to construct dose-response curves for up to 6 Gy gamma-rays. Accident simulation exercises were performed to assess the suitability of the PCC assay by detecting speed of analysis and minimum number of cells required for categorization of potentially exposed individuals. Results: Calibration data based on Giemsa-stained fragments in excess of 46 PCC were obtained by different partners using galleries of PCC images for each dose-point. Mean values derived from all scores yielded a linear dose-response with approximately 4 excess-fragments/cell/Gy. To unify scoring criteria, exercises were carried out using coded PCC-slides and/or coded irradiated blood samples. Analysis of samples received 24h post-exposure was successfully performed using Giemsa staining (1 excess-fragment/cell/Gy) or centromere/telomere FISH-staining for dicentrics. Conclusions: Dose assessments by RENEB partners using appropriate calibration curves were mostly in good agreement. The PCC assay is quick and reliable for whole- or partial-body triage biodosimetry by scoring excess-fragments or dicentrics in G(0)-lymphocytes. Particularly, analysis of Giemsa-stained excess PCC-fragments is simple, inexpensive and its automation could increase throughput and scoring objectivity of the PCC assay.

Published
2017
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32. RENEB intercomparison exercises analyzing micronuclei (Cytokinesis-block Micronucleus Assay)

Author

Depuydt, Julie, Baeyens, Ans, Barnard, Stephen, Beinke, Christina, Benedek, Anett, Beukes, Philip, Buraczewska, Iwona, Darroudi, Firouz, De Sanctis, Stefania, Dominguez, Inmaculada, Monteiro Gil, Octávia, Hadjidekova, Valeria, Kis, Enikő, Kulka, Ulrike, Lista, Florigio, Lumniczky, Katalin, M’kacher, Radhia, Moquet, Jayne, Obreja, Doina, Oestreicher, Ursula, Pajic, Jelena, Pastor, Nuria, Popova, Ljubomira, Regalbuto, Elisa, Ricoul, Michelle, Sabatier, Laure, Slabbert, Jacobus, Sommer, Sylwester, Testa, Antonella, Thierens, Hubert, Wojcik, Andrzej, and Vral, Anne

Subjects
SCORING PROCEDURE, radiation accident, Quality Assurance, Health Care, micronucleus assay, POPULATION TRIAGE, RADIATION BIODOSIMETRY, HIGH-THROUGHPUT, LYMPHOCYTES, Sensitivity and Specificity, VALIDATION, Radiation Monitoring, Humans, Lymphocytes, IMAGE-ANALYSIS, BIOLOGICAL DOSIMETRY, Chromosome Aberrations, Micronucleus Tests, Biology and Life Sciences, Biodosimetry, Reproducibility of Results, Radiation Exposure, CYTOGENETICS, Europe, EUROPEAN NETWORK, Biological Assay, triage, RENEB
Abstract

Purpose: In the framework of the ‘Realizing the European Network of Biodosimetry’ (RENEB) project, two intercomparison exercises were conducted to assess the suitability of an optimized version of the cytokinesis-block micronucleus assay, and to evaluate the capacity of a large laboratory network performing biodosimetry for radiation emergency triages. Twelve European institutions participated in the first exercise, and four non-RENEB labs were added in the second one. Materials and methods: Irradiated blood samples were shipped to participating labs, whose task was to culture these samples and provide a blind dose estimate. Micronucleus analysis was performed by automated, semi-automated and manual procedures. Results: The dose estimates provided by network laboratories were in good agreement with true administered doses. The most accurate estimates were reported for low dose points (=< 0.94 Gy). For higher dose points (>= 2.7 Gy) a larger variation in estimates was observed, though in the second exercise the number of acceptable estimates increased satisfactorily. Higher accuracy was achieved with the semi-automated method. Conclusion: The results of the two exercises performed by our network demonstrate that the micronucleus assay is a useful tool for large-scale radiation emergencies, and can be successfully implemented within a large network of laboratories.

Published
2016

33. Dose assessment intercomparisons within the RENEB network using G0-lymphocyte prematurely condensed chromosomes (PCC assay)

Author

Terzoudi, Georgia I., primary, Pantelias, Gabriel, additional, Darroudi, Firouz, additional, Barszczewska, Katarzyna, additional, Buraczewska, Iwona, additional, Depuydt, Julie, additional, Georgieva, Dimka, additional, Hadjidekova, Valeria, additional, Hatzi, Vasiliki I., additional, Karachristou, Ioanna, additional, Karakosta, Maria, additional, Meschini, Roberta, additional, M’Kacher, Radhia, additional, Montoro, Alegria, additional, Palitti, Fabrizio, additional, Pantelias, Antonio, additional, Pepe, Gaetano, additional, Ricoul, Michelle, additional, Sabatier, Laure, additional, Sebastià, Natividad, additional, Sommer, Sylwester, additional, Vral, Anne, additional, Zafiropoulos, Demetre, additional, and Wojcik, Andrzej, additional

Published
2016
Full Text
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34. RENEB biodosimetry intercomparison analyzing translocations by FISH

Author

Barquinero, Joan Francesc, primary, Beinke, Christina, additional, Borràs, Mireia, additional, Buraczewska, Iwona, additional, Darroudi, Firouz, additional, Gregoire, Eric, additional, Hristova, Rositsa, additional, Kulka, Ulrike, additional, Lindholm, Carita, additional, Moreno, Mercedes, additional, Moquet, Jayne, additional, Oestreicher, Ursula, additional, Prieto, M Jesús, additional, Pujol, Mònica, additional, Ricoul, Michelle, additional, Sabatier, Laure, additional, Sommer, Sylwester, additional, Sun, Mingzhu, additional, Wojcik, Andrzej, additional, and Barrios, Leonardo, additional

Published
2016
Full Text
View/download PDF

36. Assessing the Carcinogenic Potential of Low Dose Exposures to Chemical Mixtures in the Environment: Replicative immortality

Author

80402890, Goodson, William H., Lowe, Leroy, Carpenter, O. David, Gilbertson, Michael, Manaf Ali, Abdul, Lopez de Cerain Salsamendi, Adela, Lasfar, Ahmed, Carnero, Amancio, Azqueta, Amaya, Amedei, Amedeo, Charles, K. Amelia, Laird, Dale W., Koch, C. Daniel, Carlin, J. Danielle, Felsher, W. Dean, Roy, Debasish, Brown, G. Dustin, Ratovitski, Edward, Ryan, P. Elizabeth, Corsini, Emanuela, Rojas, Emilio, Manjili, H. Masoud, Moon, Eun-Yi, Laconi, Ezio, Marongiu, Fabio, Al-Mulla, Fahd, Chiaradonna, Ferdinando, Darroudi, Firouz, Martin, Francis L., Van Schooten, J. Frederik, Goldberg, S. Gary, Wagemaker, Gerard, Lleonart, E. Matilde, Nangami, N. Gladys, Calaf, M. Gloria, Williams, P. Graeme, Wolf, T. Gregory, Koppen, Gudrun, Brunborg, Gunnar, Lyerly, H. Kim, Krishnan, Harini, Ab Hamid, Hasiah, Yasaei, Hemad, Xia, Menghang, Sone, Hideko, Kondoh, Hiroshi, Salem, K. Hosni, Hsu, Hsue-Yin, Park, Hyun Ho, Koturbash, Igor, Miousse, R. Isabelle, Scovassi, A.Ivana, Klaunig, E. James, Vondráček, Jan, Gonzalez Guzman, J. Michael, Raju, Jayadev, Roman, Jesse, Wise, John Pierce, Whitfield, R. Jonathan, Woodrick, Jordan, Christopher, A. Joseph, Ochieng, Josiah, Martinez-Leal, Juan Fernando, Weisz, Judith, Kravchenko, Julia, Karamouzis, V. Michalis, Sun, Jun, Prudhomme, R. Kalan, Narayanan, Kannan Badri, Cohen-Solal, A. Karine, Moorwood, Kim, Gonzalez, Laetitia, Soucek, Laura, Jian, Le, D’Abronzo, S. Leandro, Lin, Liang-Tzung, Kirsch-Volders, Micheline, Li, Lin, Gulliver, Linda, McCawley, J. Lisa, Memeo, Lorenzo, Vermeulen, Louis, Leyns, Luc, Zhang, Luoping, Valverde, Mahara, Khatami, Mahin, Romano, Maria Fiammetta, Vaccari, Monica, Chapellier, Marion, Williams, A. Marc, Wade, Mark, Kuemmerle, B. Nancy, Singh, Neetu, Cruickshanks, Nichola, Collins, R. Andrew, Kleinstreuer, Nicole, van Larebeke, Nik, Ahmed, Nuzhat, Ogunkua, Olugbemiga, Krishnakumar, P. K., Vadgama, Pankaj, Marignani, A. Paola, Ghosh, M. Paramita, Ostrosky-Wegman, Patricia, Thompson, A. Patricia, Ward, Andrew, Dent, Paul, Heneberg, Petr, Darbre, Philippa, Leung, Po Sing, Nangia-Makker, Pratima, Cheng, Qiang (Shawn), Robey, R. Brooks, Al-Temaimi, Rabeah, Roy, Rabindra, Andrade-Vieira, Rafaela, Salzberg, C. Anna, Sinha, K. Ranjeet, Mehta, Rekha, Vento, Renza, Di Fiore, Riccardo, Ponce-Cusi, Richard, Dornetshuber-Fleiss, Rita, Nahta, Rita, Castellino, C. Robert, Palorini, Roberta, Hamid, A. Roslida, Colacci, Anna Maria, Langie, A. S. Sabine, Eltom, E. Sakina, Brooks, A. Samira, Ryeom, Sandra, Wise, S. Sandra, Bay, N. Sarah, Harris, A. Shelley, Papagerakis, Silvana, Romano, Simona, Pavanello, Sofia, Olsen, Ann-Karin, Eriksson, Staffan, Forte, Stefano, Casey, C. Stephanie, Luanpitpong, Sudjit, Lee, Tae-Jin, Otsuki, Takemi, Chen, Tao, Massfelder, Thierry, Sanderson, Thomas, Guarnieri, Tiziana, Berg, Arthur, Hultman, Tove, Dormoy, Valérian, Odero-Marah, Valerie, Sabbisetti, Venkata, Maguer-Satta, Veronique, Rathmell, W.Kimryn, Engström, Wilhelm, Decker, K. William, Bisson, H. William, Rojanasakul, Yon, Barclay, J. Barry, Luqmani, Yunus, Chen, Zhenbang, Hu, Zhiwei, Zhou, P. Binhua, Blanco-Aparicio, Carmen, Baglole, J. Carolyn, Dong, Chenfang, Mondello, Chiara, Hsu, Chia-Wen, Naus, C. Christian, Yedjou, Clement, Curran, S. Colleen, 80402890, Goodson, William H., Lowe, Leroy, Carpenter, O. David, Gilbertson, Michael, Manaf Ali, Abdul, Lopez de Cerain Salsamendi, Adela, Lasfar, Ahmed, Carnero, Amancio, Azqueta, Amaya, Amedei, Amedeo, Charles, K. Amelia, Laird, Dale W., Koch, C. Daniel, Carlin, J. Danielle, Felsher, W. Dean, Roy, Debasish, Brown, G. Dustin, Ratovitski, Edward, Ryan, P. Elizabeth, Corsini, Emanuela, Rojas, Emilio, Manjili, H. Masoud, Moon, Eun-Yi, Laconi, Ezio, Marongiu, Fabio, Al-Mulla, Fahd, Chiaradonna, Ferdinando, Darroudi, Firouz, Martin, Francis L., Van Schooten, J. Frederik, Goldberg, S. Gary, Wagemaker, Gerard, Lleonart, E. Matilde, Nangami, N. Gladys, Calaf, M. Gloria, Williams, P. Graeme, Wolf, T. Gregory, Koppen, Gudrun, Brunborg, Gunnar, Lyerly, H. Kim, Krishnan, Harini, Ab Hamid, Hasiah, Yasaei, Hemad, Xia, Menghang, Sone, Hideko, Kondoh, Hiroshi, Salem, K. Hosni, Hsu, Hsue-Yin, Park, Hyun Ho, Koturbash, Igor, Miousse, R. Isabelle, Scovassi, A.Ivana, Klaunig, E. James, Vondráček, Jan, Gonzalez Guzman, J. Michael, Raju, Jayadev, Roman, Jesse, Wise, John Pierce, Whitfield, R. Jonathan, Woodrick, Jordan, Christopher, A. Joseph, Ochieng, Josiah, Martinez-Leal, Juan Fernando, Weisz, Judith, Kravchenko, Julia, Karamouzis, V. Michalis, Sun, Jun, Prudhomme, R. Kalan, Narayanan, Kannan Badri, Cohen-Solal, A. Karine, Moorwood, Kim, Gonzalez, Laetitia, Soucek, Laura, Jian, Le, D’Abronzo, S. Leandro, Lin, Liang-Tzung, Kirsch-Volders, Micheline, Li, Lin, Gulliver, Linda, McCawley, J. Lisa, Memeo, Lorenzo, Vermeulen, Louis, Leyns, Luc, Zhang, Luoping, Valverde, Mahara, Khatami, Mahin, Romano, Maria Fiammetta, Vaccari, Monica, Chapellier, Marion, Williams, A. Marc, Wade, Mark, Kuemmerle, B. Nancy, Singh, Neetu, Cruickshanks, Nichola, Collins, R. Andrew, Kleinstreuer, Nicole, van Larebeke, Nik, Ahmed, Nuzhat, Ogunkua, Olugbemiga, Krishnakumar, P. K., Vadgama, Pankaj, Marignani, A. Paola, Ghosh, M. Paramita, Ostrosky-Wegman, Patricia, Thompson, A. Patricia, Ward, Andrew, Dent, Paul, Heneberg, Petr, Darbre, Philippa, Leung, Po Sing, Nangia-Makker, Pratima, Cheng, Qiang (Shawn), Robey, R. Brooks, Al-Temaimi, Rabeah, Roy, Rabindra, Andrade-Vieira, Rafaela, Salzberg, C. Anna, Sinha, K. Ranjeet, Mehta, Rekha, Vento, Renza, Di Fiore, Riccardo, Ponce-Cusi, Richard, Dornetshuber-Fleiss, Rita, Nahta, Rita, Castellino, C. Robert, Palorini, Roberta, Hamid, A. Roslida, Colacci, Anna Maria, Langie, A. S. Sabine, Eltom, E. Sakina, Brooks, A. Samira, Ryeom, Sandra, Wise, S. Sandra, Bay, N. Sarah, Harris, A. Shelley, Papagerakis, Silvana, Romano, Simona, Pavanello, Sofia, Olsen, Ann-Karin, Eriksson, Staffan, Forte, Stefano, Casey, C. Stephanie, Luanpitpong, Sudjit, Lee, Tae-Jin, Otsuki, Takemi, Chen, Tao, Massfelder, Thierry, Sanderson, Thomas, Guarnieri, Tiziana, Berg, Arthur, Hultman, Tove, Dormoy, Valérian, Odero-Marah, Valerie, Sabbisetti, Venkata, Maguer-Satta, Veronique, Rathmell, W.Kimryn, Engström, Wilhelm, Decker, K. William, Bisson, H. William, Rojanasakul, Yon, Barclay, J. Barry, Luqmani, Yunus, Chen, Zhenbang, Hu, Zhiwei, Zhou, P. Binhua, Blanco-Aparicio, Carmen, Baglole, J. Carolyn, Dong, Chenfang, Mondello, Chiara, Hsu, Chia-Wen, Naus, C. Christian, Yedjou, Clement, and Curran, S. Colleen

Abstract

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Published
2015

37. Causes of genome instability: the effect of low dose chemical exposures in modern society

Author

Langie, Sabine A. S., Koppen, Gudrun, Desaulniers, Daniel, Al-Mulla, Fahd, Al-Temaimi, Rabeah, Amedei, Amedeo, Azqueta, Amaya, Bisson, William H., Brown, Dustin, Brunborg, Gunnar, Charles, Amelia K., Chen, Tao, Colacci, Annamaria, Darroudi, Firouz, Forte, Stefano, Gonzalez, Laetitia, A.Hamid, Roslida, Langie, Sabine A. S., Koppen, Gudrun, Desaulniers, Daniel, Al-Mulla, Fahd, Al-Temaimi, Rabeah, Amedei, Amedeo, Azqueta, Amaya, Bisson, William H., Brown, Dustin, Brunborg, Gunnar, Charles, Amelia K., Chen, Tao, Colacci, Annamaria, Darroudi, Firouz, Forte, Stefano, Gonzalez, Laetitia, and A.Hamid, Roslida

Abstract

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.

Published
2015

38. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

Author

Goodson III, William H., Lowe, Leroy, Carpenter, David O., Gilbertson, Michael, Ali, Abdul Manaf, Salsamendi, Adela Lopez de Cerain, Lasfar, Ahmed, Carnero, Amancio, Azqueta, Amaya, Amedei, Amedeo, Charles, Amelia K., Collins, Andrew R., Ward, Andrew, Salzberg, Anna C., Colacci, Anna Maria, Olsen, Ann Karin, Berg, Arthur, Barclay, Barry J., Zhou, Binhua P., Aparicio, Carmen Blanco, Baglole, Carolyn J., Dong, Chenfang, Mondello, Chiara, Chia, Wen Hsu, Naus, Christian C., Yedjou, Clement, Curran, Colleen S., Laird, Dale W., Koch, Daniel C., Carlin, Danielle J., Felsher, Dean W., Roy, Debasish, Brown, Dustin G., Ratovitski, Edward, Ryan, Elizabeth P., Corsini, Emanuela, Rojas, Emilio, Eun, Yi Moon, Laconi, Ezio, Marongiu, Fabio, Al-Mulla, Fahd, Chiaradonna, Ferdinando, Darroudi, Firouz, Martin, Francis L., Schooten, Frederik J. Van, Goldberg, Gary S., Wagemaker, Gerard, Nangami, Gladys N., Calaf, Gloria M., Williams, Graeme P., Wolf, Gregory T., Koppen, Gudrun, Brunborg, Gunnar, Lyerly, H. Kim, Krishnan, Harini, Ab. Hamid, Hasiah, Yasaei, Hemad, Sone, Hideko, Kondoh, Hiroshi, Salem, Hosni K., Hsue, Yin Hsu, Hyun, Ho Park, Koturbash, Igor, Miousse, Isabelle R., Scovassi, A. Ivana, Klaunig, James E., Vondrá ček, Jan, Raju, Jayadev, Roman, Jesse, Wise Sr., John Pierce, Whitfield, Jonathan R., Woodrick, Jordan, Christopher, Joseph A., Ochieng, Josiah, Martinez-Leal, Juan Fernando, Weisz, Judith, Kravchenko, Julia, Sun, Jun, Prudhomme, Kalan R., Narayanan, Kannan Badri, Cohen-Solal, Karine A., Moorwood, Kim, Gonzalez, Laetitia, Soucek, Laura, Jian, Le, D’Abronzo, Leandro S., Liang, Tzung Lin, Li, Lin, Gulliver, Linda, McCawley, Lisa J., Memeo, Lorenzo, Vermeulen, Louis, Leyns, Luc, Zhang, Luoping, Valverde, Mahara, Khatami, Mahin, Romano, Maria Fiammetta, Chapellier, Marion, Williams, Marc A., Wade, Mark, Manjili, Masoud H., Lleonart, Matilde E., Xia, Menghang, Gonzalez Guzma, Michael J., Karamouzis, Michalis V., Kirsch Volders, Micheline, Vaccari, Monica, Kuemmerle, Nancy B., Singh, Neetu, Cruickshanks, Nichola, Kleinstreuer, Nicole, Larebeke, Nik van, Ahmed, Nuzhat, Ogunkua, Olugbemiga, Krishnakumar, P. K., Vadgama, Pankaj, Marignani, Paola A., Ghosh, Paramita M., Ostrosky Wegman, Patricia, Thompson, Patricia A., Dent, Paul, Darbre, Philippa, Heneberg, Petr, Po, Sing Leung, Nangia Makker, Pratima, Cheng, Qiang, Robey, R. Brooks, Al-Temaimi, Rabeah, Roy, Rabindra, Andrade Vieira, Rafaela, Sinha, Ranjeet K., Mehta, Rekha, Vento, Renza, Di Fiore, Riccardo, Ponce Cusi, Richard, Dornetshuber Fleiss, Rita, Nahta, Rita, Castellino, Robert C., Palorini, Roberta, Abd Hamid @ Abdul Razak, Roslida, Langie, Sabine A. S., Eltom, Sakina E., Brooks, Samira A., Ryeom, Sandra, Wise, Sandra S., Bay, Sarah N., Harris, Shelley A., Papagerakis, Silvana, Romano, Simona, Pavanello, Sofia, Eriksson, Staffan, Forte, Stefano, Casey, Stephanie C., Luanpitpong, Sudjit, Tae, Jin Lee, Otsuki, Takemi, Chen, Tao, Massfelder, Thierry, Sanderson, Thomas, Guarnieri, Tiziana, Hultman, Tove, Dormoy, Valérian, Odero Mara, Valerie, Sabbisetti, Venkata, Maguer Satta, Veronique, Rathmell, W. Kimryn, Engström, Wilhelm, Decker, William K., Bisson, William H., Rojanasakul, Yon, Luqmani, Yunus, Chen, Zhenbang, Hu, Zhiwei, Goodson III, William H., Lowe, Leroy, Carpenter, David O., Gilbertson, Michael, Ali, Abdul Manaf, Salsamendi, Adela Lopez de Cerain, Lasfar, Ahmed, Carnero, Amancio, Azqueta, Amaya, Amedei, Amedeo, Charles, Amelia K., Collins, Andrew R., Ward, Andrew, Salzberg, Anna C., Colacci, Anna Maria, Olsen, Ann Karin, Berg, Arthur, Barclay, Barry J., Zhou, Binhua P., Aparicio, Carmen Blanco, Baglole, Carolyn J., Dong, Chenfang, Mondello, Chiara, Chia, Wen Hsu, Naus, Christian C., Yedjou, Clement, Curran, Colleen S., Laird, Dale W., Koch, Daniel C., Carlin, Danielle J., Felsher, Dean W., Roy, Debasish, Brown, Dustin G., Ratovitski, Edward, Ryan, Elizabeth P., Corsini, Emanuela, Rojas, Emilio, Eun, Yi Moon, Laconi, Ezio, Marongiu, Fabio, Al-Mulla, Fahd, Chiaradonna, Ferdinando, Darroudi, Firouz, Martin, Francis L., Schooten, Frederik J. Van, Goldberg, Gary S., Wagemaker, Gerard, Nangami, Gladys N., Calaf, Gloria M., Williams, Graeme P., Wolf, Gregory T., Koppen, Gudrun, Brunborg, Gunnar, Lyerly, H. Kim, Krishnan, Harini, Ab. Hamid, Hasiah, Yasaei, Hemad, Sone, Hideko, Kondoh, Hiroshi, Salem, Hosni K., Hsue, Yin Hsu, Hyun, Ho Park, Koturbash, Igor, Miousse, Isabelle R., Scovassi, A. Ivana, Klaunig, James E., Vondrá ček, Jan, Raju, Jayadev, Roman, Jesse, Wise Sr., John Pierce, Whitfield, Jonathan R., Woodrick, Jordan, Christopher, Joseph A., Ochieng, Josiah, Martinez-Leal, Juan Fernando, Weisz, Judith, Kravchenko, Julia, Sun, Jun, Prudhomme, Kalan R., Narayanan, Kannan Badri, Cohen-Solal, Karine A., Moorwood, Kim, Gonzalez, Laetitia, Soucek, Laura, Jian, Le, D’Abronzo, Leandro S., Liang, Tzung Lin, Li, Lin, Gulliver, Linda, McCawley, Lisa J., Memeo, Lorenzo, Vermeulen, Louis, Leyns, Luc, Zhang, Luoping, Valverde, Mahara, Khatami, Mahin, Romano, Maria Fiammetta, Chapellier, Marion, Williams, Marc A., Wade, Mark, Manjili, Masoud H., Lleonart, Matilde E., Xia, Menghang, Gonzalez Guzma, Michael J., Karamouzis, Michalis V., Kirsch Volders, Micheline, Vaccari, Monica, Kuemmerle, Nancy B., Singh, Neetu, Cruickshanks, Nichola, Kleinstreuer, Nicole, Larebeke, Nik van, Ahmed, Nuzhat, Ogunkua, Olugbemiga, Krishnakumar, P. K., Vadgama, Pankaj, Marignani, Paola A., Ghosh, Paramita M., Ostrosky Wegman, Patricia, Thompson, Patricia A., Dent, Paul, Darbre, Philippa, Heneberg, Petr, Po, Sing Leung, Nangia Makker, Pratima, Cheng, Qiang, Robey, R. Brooks, Al-Temaimi, Rabeah, Roy, Rabindra, Andrade Vieira, Rafaela, Sinha, Ranjeet K., Mehta, Rekha, Vento, Renza, Di Fiore, Riccardo, Ponce Cusi, Richard, Dornetshuber Fleiss, Rita, Nahta, Rita, Castellino, Robert C., Palorini, Roberta, Abd Hamid @ Abdul Razak, Roslida, Langie, Sabine A. S., Eltom, Sakina E., Brooks, Samira A., Ryeom, Sandra, Wise, Sandra S., Bay, Sarah N., Harris, Shelley A., Papagerakis, Silvana, Romano, Simona, Pavanello, Sofia, Eriksson, Staffan, Forte, Stefano, Casey, Stephanie C., Luanpitpong, Sudjit, Tae, Jin Lee, Otsuki, Takemi, Chen, Tao, Massfelder, Thierry, Sanderson, Thomas, Guarnieri, Tiziana, Hultman, Tove, Dormoy, Valérian, Odero Mara, Valerie, Sabbisetti, Venkata, Maguer Satta, Veronique, Rathmell, W. Kimryn, Engström, Wilhelm, Decker, William K., Bisson, William H., Rojanasakul, Yon, Luqmani, Yunus, Chen, Zhenbang, and Hu, Zhiwei

Abstract

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

Published
2015

39. Causes of genome instability:the effect of low dose chemical exposures in modern society

Author

Langie, Sabine A S, Koppen, Gudrun, Desaulniers, Daniel, Al-Mulla, Fahd, Al-Temaimi, Rabeah, Amedei, Amedeo, Azqueta, Amaya, Bisson, William H, Brown, Dustin G, Brunborg, Gunnar, Charles, Amelia K, Chen, Tao, Colacci, Annamaria, Darroudi, Firouz, Forte, Stefano, Gonzalez, Laetitia, Hamid, Roslida A, Knudsen, Lisbeth E, Leyns, Luc, Lopez de Cerain Salsamendi, Adela, Memeo, Lorenzo, Mondello, Chiara, Mothersill, Carmel, Olsen, Ann-Karin, Pavanello, Sofia, Raju, Jayadev, Rojas, Emilio, Roy, Rabindra, Ryan, Elizabeth P, Ostrosky-Wegman, Patricia, Salem, Hosni K, Scovassi, A Ivana, Singh, Neetu, Vaccari, Monica, Van Schooten, Frederik J, Valverde, Mahara, Woodrick, Jordan, Zhang, Luoping, van Larebeke, Nik, Kirsch-Volders, Micheline, Collins, Andrew R, Langie, Sabine A S, Koppen, Gudrun, Desaulniers, Daniel, Al-Mulla, Fahd, Al-Temaimi, Rabeah, Amedei, Amedeo, Azqueta, Amaya, Bisson, William H, Brown, Dustin G, Brunborg, Gunnar, Charles, Amelia K, Chen, Tao, Colacci, Annamaria, Darroudi, Firouz, Forte, Stefano, Gonzalez, Laetitia, Hamid, Roslida A, Knudsen, Lisbeth E, Leyns, Luc, Lopez de Cerain Salsamendi, Adela, Memeo, Lorenzo, Mondello, Chiara, Mothersill, Carmel, Olsen, Ann-Karin, Pavanello, Sofia, Raju, Jayadev, Rojas, Emilio, Roy, Rabindra, Ryan, Elizabeth P, Ostrosky-Wegman, Patricia, Salem, Hosni K, Scovassi, A Ivana, Singh, Neetu, Vaccari, Monica, Van Schooten, Frederik J, Valverde, Mahara, Woodrick, Jordan, Zhang, Luoping, van Larebeke, Nik, Kirsch-Volders, Micheline, and Collins, Andrew R

Abstract

Genome instability is a prerequisite for the development of cancer. It occurs when genome maintenance systems fail to safeguard the genome's integrity, whether as a consequence of inherited defects or induced via exposure to environmental agents (chemicals, biological agents and radiation). Thus, genome instability can be defined as an enhanced tendency for the genome to acquire mutations; ranging from changes to the nucleotide sequence to chromosomal gain, rearrangements or loss. This review raises the hypothesis that in addition to known human carcinogens, exposure to low dose of other chemicals present in our modern society could contribute to carcinogenesis by indirectly affecting genome stability. The selected chemicals with their mechanisms of action proposed to indirectly contribute to genome instability are: heavy metals (DNA repair, epigenetic modification, DNA damage signaling, telomere length), acrylamide (DNA repair, chromosome segregation), bisphenol A (epigenetic modification, DNA damage signaling, mitochondrial function, chromosome segregation), benomyl (chromosome segregation), quinones (epigenetic modification) and nano-sized particles (epigenetic pathways, mitochondrial function, chromosome segregation, telomere length). The purpose of this review is to describe the crucial aspects of genome instability, to outline the ways in which environmental chemicals can affect this cancer hallmark and to identify candidate chemicals for further study. The overall aim is to make scientists aware of the increasing need to unravel the underlying mechanisms via which chemicals at low doses can induce genome instability and thus promote carcinogenesis.

Published
2015

40. Human fetal/tumor metakaryotic stem cells: pangenomic homologous pairing and telomeric end-joining of chromatids

Author

Massachusetts Institute of Technology. Department of Biological Engineering, MIT Edgerton Center, Gruhl, Amanda Natalie, Gostjeva, Elena V., Thilly, William G., Fomina, Janna N., Darroudi, Firouz, Thilly, William G, Massachusetts Institute of Technology. Department of Biological Engineering, MIT Edgerton Center, Gruhl, Amanda Natalie, Gostjeva, Elena V., Thilly, William G., Fomina, Janna N., Darroudi, Firouz, and Thilly, William G

Abstract

Metakaryotic cells and syncytia with large, hollow, bell-shaped nuclei demonstrate symmetrical and asymmetrical amitotic nuclear fissions in microanatomical positions and numbers expected of stem cell lineages in tissues of all three primordial germ layers and their derived tumors. Using fluorescence in situ hybridization, mononuclear metakaryotic interphase cells have been found with only 23 centromeric and 23 telomeric staining regions. Syncytial bell-shaped nuclei found approximately during weeks 5–12 of human gestation display 23 centromeric and either 23 or 46 telomeric staining regions. These images suggest that (1) homologous chromatids pair at centromeres and telomeres, (2) all paired telomeres join end-to-end with other paired telomeres in all mononuclear and some syncytial metakaryotic cells, and (3) telomere junctions may open and close during the syncytial phase of development. Twenty-three telomeric joining figures could be accounted by 23 rings of one chromatid pair each, a single pangenomic ring of 23 joined chromatid pairs, or any of many possible sets of oligo-chromatid pair rings. As telomeric end-joining may affect peri-telomeric gene expression, a programmed sequence of telomeric end-joining associations in metakaryotic stem cells could guide developmental arboration and errors in, or interruptions of, this program could contribute to carcinogenesis., National Institute of Environmental Health Sciences, United Therapeutics, Inc.

Published
2015

42. Metakaryotic stem cell nuclei use pangenomic dsRNA/DNA intermediates in genome replication and segregation

Author

Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Thilly, William G., Gostjeva, Elena V., Koledova, Vera V., Zukerberg, Lawrence R, Chung, Daniel, Fomina, Janna N, Darroudi, Firouz, Stollar, B David, Koledova, Vera V, Thilly, William G, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Thilly, William G., Gostjeva, Elena V., Koledova, Vera V., Zukerberg, Lawrence R, Chung, Daniel, Fomina, Janna N, Darroudi, Firouz, Stollar, B David, Koledova, Vera V, and Thilly, William G

Abstract

Bell shaped nuclei of metakaryotic cells double their DNA content during and after symmetric and asymmetric amitotic fissions rather than in the separate, pre-mitotic S-phase of eukaryotic cells. A parsimonious hypothesis was tested that the two anti-parallel strands of each chromatid DNA helix were first segregated as ssDNA-containing complexes into sister nuclei then copied to recreate a dsDNA genome. Metakaryotic nuclei that were treated during amitosis with RNase A and stained with acridine orange or fluorescent antibody to ssDNA revealed large amounts of ssDNA. Without RNase treatment metakaryotic nuclei in amitosis stained strongly with an antibody complex specific to dsRNA/DNA. Images of amitotic figures co-stained with dsRNA/DNA antibody and DAPI indicated that the entire interphase dsDNA genome (B-form helices) was transformed into two dsRNA/DNA genomes (A-form helices) that were segregated in the daughter cell nuclei then retransformed into dsDNA. As this process segregates DNA strands of opposite polarity in sister cells it hypothetically offers a sequential switching mechanism within the diverging stem cell lineages of development.

Published
2014

43. Dose assessment intercomparisons within the RENEB network using G 0 -lymphocyte prematurely condensed chromosomes (PCC assay).

Author

Terzoudi, Georgia I., Pantelias, Gabriel, Darroudi, Firouz, Barszczewska, Katarzyna, Buraczewska, Iwona, Depuydt, Julie, Georgieva, Dimka, Hadjidekova, Valeria, Hatzi, Vasiliki I., Karachristou, Ioanna, Karakosta, Maria, Meschini, Roberta, M'Kacher, Radhia, Montoro, Alegria, Palitti, Fabrizio, Pantelias, Antonio, Pepe, Gaetano, Ricoul, Michelle, Sabatier, Laure, and Sebastià, Natividad

Subjects
RADIATION protection, LYMPHOCYTES, PREMATURE chromosome condensation, PEPTIDE nucleic acids, CELL fusion
Abstract

Purpose: Dose assessment intercomparisons within the RENEB network were performed for triage biodosimetry analyzing G0-lymphocyte PCC for harmonization, standardization and optimization of the PCC assay. Materials and methods: Comparative analysis among different partners for dose assessment included shipment of PCC-slides and captured images to construct dose-response curves for up to 6 Gy γ-rays. Accident simulation exercises were performed to assess the suitability of the PCC assay by detecting speed of analysis and minimum number of cells required for categorization of potentially exposed individuals. Results: Calibration data based on Giemsa-stained fragments in excess of 46 PCC were obtained by different partners using galleries of PCC images for each dose-point. Mean values derived from all scores yielded a linear dose-response with approximately 4 excess-fragments/cell/Gy. To unify scoring criteria, exercises were carried out using coded PCC-slides and/or coded irradiated blood samples. Analysis of samples received 24 h post-exposure was successfully performed using Giemsa staining (1 excess-fragment/cell/Gy) or centromere/telomere FISH-staining for dicentrics. Conclusions: Dose assessments by RENEB partners using appropriate calibration curves were mostly in good agreement. The PCC assay is quick and reliable for whole- or partial-body triage biodosimetry by scoring excess-fragments or dicentrics in G0-lymphocytes. Particularly, analysis of Giemsa-stained excess PCC-fragments is simple, inexpensive and its automation could increase throughput and scoring objectivity of the PCC assay. [ABSTRACT FROM AUTHOR]

Published
2017
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49. A novel radiosensitive SCID patient with a pronounced G2/M sensitivity

Author

Wiegant, Wouter W., primary, Meyers, Matty, additional, Verkaik, Nicole S., additional, van der Burg, Mirjam, additional, Darroudi, Firouz, additional, Romeijn, Ron, additional, Bernatowska, Ewa, additional, Wolska-Kusnierz, Beata, additional, Mikoluc, Bozena, additional, Jaspers, Nicolaas G.J., additional, Vreeken, Cees, additional, Ijspeert, Hanna, additional, Esveldt-van Lange, Rebecca E.E., additional, Friedl, Anna A., additional, de Villartay, Jean-Pierre, additional, Mullenders, Leon H.F., additional, van Dongen, Jacques J.M., additional, van Gent, Dik C., additional, Pastink, Albert, additional, and Zdzienicka, Małgorzata Z., additional

Published
2010
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