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Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead
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 betwe...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480130/ https://www.ncbi.nlm.nih.gov/pubmed/26106142 http://dx.doi.org/10.1093/carcin/bgv039 |
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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, Anna Maria 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 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. 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. Wade, Mark Manjili, Masoud H. Lleonart, Matilde E. Xia, Menghang Gonzalez Guzman, Michael J. Karamouzis, Michalis V. Kirsch-Volders, Micheline Vaccari, Monica Kuemmerle, Nancy B. Singh, Neetu Cruickshanks, Nichola Kleinstreuer, Nicole van Larebeke, Nik Ahmed, Nuzhat Ogunkua, Olugbemiga Krishnakumar, P.K. Vadgama, Pankaj Marignani, Paola A. Ghosh, Paramita M. Ostrosky-Wegman, Patricia Thompson, Patricia A. 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 Sinha, Ranjeet K. Mehta, Rekha Vento, Renza Di Fiore, Riccardo Ponce-Cusi, Richard Dornetshuber-Fleiss, Rita Nahta, Rita Castellino, Robert C. Palorini, Roberta Hamid, Roslida A. 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 Lee, Tae-Jin Otsuki, Takemi Chen, Tao Massfelder, Thierry Sanderson, Thomas Guarnieri, Tiziana Hultman, Tove Dormoy, Valérian Odero-Marah, 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 |
author_facet | 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, Anna Maria 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 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. 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. Wade, Mark Manjili, Masoud H. Lleonart, Matilde E. Xia, Menghang Gonzalez Guzman, Michael J. Karamouzis, Michalis V. Kirsch-Volders, Micheline Vaccari, Monica Kuemmerle, Nancy B. Singh, Neetu Cruickshanks, Nichola Kleinstreuer, Nicole van Larebeke, Nik Ahmed, Nuzhat Ogunkua, Olugbemiga Krishnakumar, P.K. Vadgama, Pankaj Marignani, Paola A. Ghosh, Paramita M. Ostrosky-Wegman, Patricia Thompson, Patricia A. 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 Sinha, Ranjeet K. Mehta, Rekha Vento, Renza Di Fiore, Riccardo Ponce-Cusi, Richard Dornetshuber-Fleiss, Rita Nahta, Rita Castellino, Robert C. Palorini, Roberta Hamid, Roslida A. 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 Lee, Tae-Jin Otsuki, Takemi Chen, Tao Massfelder, Thierry Sanderson, Thomas Guarnieri, Tiziana Hultman, Tove Dormoy, Valérian Odero-Marah, 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 |
author_sort | Goodson, William H. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4480130 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44801302015-06-26 Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead 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, Anna Maria 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 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. 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. Wade, Mark Manjili, Masoud H. Lleonart, Matilde E. Xia, Menghang Gonzalez Guzman, Michael J. Karamouzis, Michalis V. Kirsch-Volders, Micheline Vaccari, Monica Kuemmerle, Nancy B. Singh, Neetu Cruickshanks, Nichola Kleinstreuer, Nicole van Larebeke, Nik Ahmed, Nuzhat Ogunkua, Olugbemiga Krishnakumar, P.K. Vadgama, Pankaj Marignani, Paola A. Ghosh, Paramita M. Ostrosky-Wegman, Patricia Thompson, Patricia A. 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 Sinha, Ranjeet K. Mehta, Rekha Vento, Renza Di Fiore, Riccardo Ponce-Cusi, Richard Dornetshuber-Fleiss, Rita Nahta, Rita Castellino, Robert C. Palorini, Roberta Hamid, Roslida A. 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 Lee, Tae-Jin Otsuki, Takemi Chen, Tao Massfelder, Thierry Sanderson, Thomas Guarnieri, Tiziana Hultman, Tove Dormoy, Valérian Odero-Marah, 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 Carcinogenesis Review 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. Oxford University Press 2015-06 2015-06-19 /pmc/articles/PMC4480130/ /pubmed/26106142 http://dx.doi.org/10.1093/carcin/bgv039 Text en © The Author 2015. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Review 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, Anna Maria 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 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. 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. Wade, Mark Manjili, Masoud H. Lleonart, Matilde E. Xia, Menghang Gonzalez Guzman, Michael J. Karamouzis, Michalis V. Kirsch-Volders, Micheline Vaccari, Monica Kuemmerle, Nancy B. Singh, Neetu Cruickshanks, Nichola Kleinstreuer, Nicole van Larebeke, Nik Ahmed, Nuzhat Ogunkua, Olugbemiga Krishnakumar, P.K. Vadgama, Pankaj Marignani, Paola A. Ghosh, Paramita M. Ostrosky-Wegman, Patricia Thompson, Patricia A. 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 Sinha, Ranjeet K. Mehta, Rekha Vento, Renza Di Fiore, Riccardo Ponce-Cusi, Richard Dornetshuber-Fleiss, Rita Nahta, Rita Castellino, Robert C. Palorini, Roberta Hamid, Roslida A. 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 Lee, Tae-Jin Otsuki, Takemi Chen, Tao Massfelder, Thierry Sanderson, Thomas Guarnieri, Tiziana Hultman, Tove Dormoy, Valérian Odero-Marah, 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 Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead |
title | Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead |
title_full | Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead |
title_fullStr | Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead |
title_full_unstemmed | Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead |
title_short | Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead |
title_sort | assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4480130/ https://www.ncbi.nlm.nih.gov/pubmed/26106142 http://dx.doi.org/10.1093/carcin/bgv039 |
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