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.
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | S254-S296 |
| Fachzeitschrift | Carcinogenesis |
| Jahrgang | 36 |
| Ausgabenummer | Suppl 1 |
| DOIs | |
| Publikationsstatus | Veröffentlicht - Juni 2015 |
ÖFOS 2012
- 302055 Onkologie
UN SDGs
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Goodson, W. H., Lowe, L., Carpenter, D. O., Gilbertson, M., Manaf Ali, A., Lopez de Cerain Salsamendi, A., Lasfar, A., Carnero, A., Azqueta, A., Amedei, A., Charles, A. K., Collins, A. R., Ward, A., Salzberg, A. C., Colacci, A., Olsen, A-K., Berg, A., Barclay, B. J., Zhou, B. P., ... Hu, Z. (2015). Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis, 36 (Suppl 1), S254-S296. https://doi.org/10.1093/carcin/bgv039
Goodson, William H ; Lowe, Leroy ; Carpenter, David O et al. / Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment : the challenge ahead. in: Carcinogenesis. 2015 ; Band 36 , Nr. Suppl 1. S. S254-S296.
@article{530bd85b93674172b2634f3b9c36c19f,
title = "Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead",
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.",
keywords = "Animals, Carcinogenesis, Carcinogens, Environmental, Environmental Exposure, Hazardous Substances, Humans, Neoplasms",
author = "Goodson, {William H} and Leroy Lowe and Carpenter, {David O} and Michael Gilbertson and {Manaf Ali}, Abdul and {Lopez de Cerain Salsamendi}, Adela and Ahmed Lasfar and Amancio Carnero and Amaya Azqueta and Amedeo Amedei and Charles, {Amelia K} and Collins, {Andrew R} and Andrew Ward and Salzberg, {Anna C} and Annamaria Colacci and Ann-Karin Olsen and Arthur Berg and Barclay, {Barry J} and Zhou, {Binhua P} and Carmen Blanco-Aparicio and Baglole, {Carolyn J} and Chenfang Dong and Chiara Mondello and Chia-Wen Hsu and Naus, {Christian C} and Clement Yedjou and Curran, {Colleen S} and Laird, {Dale W} and Koch, {Daniel C} and Carlin, {Danielle J} and Felsher, {Dean W} and Debasish Roy and Brown, {Dustin G} and Edward Ratovitski and Ryan, {Elizabeth P} and Emanuela Corsini and Emilio Rojas and Eun-Yi Moon and Ezio Laconi and Fabio Marongiu and Fahd Al-Mulla and Ferdinando Chiaradonna and Firouz Darroudi and Martin, {Francis L} and {Van Schooten}, {Frederik J} and Goldberg, {Gary S} and Gerard Wagemaker and Nangami, {Gladys N} and Calaf, {Gloria M} and Graeme Williams and Wolf, {Gregory T} and Gudrun Koppen and Gunnar Brunborg and Lyerly, {H Kim} and Harini Krishnan and {Ab Hamid}, Hasiah and Hemad Yasaei and Hideko Sone and Hiroshi Kondoh and Salem, {Hosni K} and Hsue-Yin Hsu and Park, {Hyun Ho} and Igor Koturbash and Miousse, {Isabelle R} and Scovassi, {A Ivana} and Klaunig, {James E} and Jan Vondr{\'a}{\v c}ek and Jayadev Raju and Jesse Roman and Wise, {John Pierce} and Whitfield, {Jonathan R} and Jordan Woodrick and Christopher, {Joseph A} and Josiah Ochieng and Martinez-Leal, {Juan Fernando} and Judith Weisz and Julia Kravchenko and Jun Sun and Prudhomme, {Kalan R} and Narayanan, {Kannan Badri} and Cohen-Solal, {Karine A} and Kim Moorwood and Laetitia Gonzalez and Laura Soucek and Le Jian and D'Abronzo, {Leandro S} and Liang-Tzung Lin and Lin Li and Linda Gulliver and McCawley, {Lisa J} and Lorenzo Memeo and Louis Vermeulen and Luc Leyns and Luoping Zhang and Mahara Valverde and Mahin Khatami and Romano, {Maria Fiammetta} and Marion Chapellier and Williams, {Marc A} and Mark Wade and Manjili, {Masoud H} and Lleonart, {Matilde E} and Menghang Xia and Gonzalez, {Michael J} and Karamouzis, {Michalis V} and Micheline Kirsch-Volders and Monica Vaccari and Kuemmerle, {Nancy B} and Neetu Singh and Nichola Cruickshanks and Nicole Kleinstreuer and {van Larebeke}, Nik and Nuzhat Ahmed and Olugbemiga Ogunkua and Krishnakumar, {P K} and Pankaj Vadgama and Marignani, {Paola A} and Ghosh, {Paramita M} and Patricia Ostrosky-Wegman and Thompson, {Patricia A} and Paul Dent and Petr Heneberg and Philippa Darbre and {Sing Leung}, Po and Pratima Nangia-Makker and Cheng, {Qiang Shawn} and Robey, {R Brooks} and Rabeah Al-Temaimi and Rabindra Roy and Rafaela Andrade-Vieira and Sinha, {Ranjeet K} and Rekha Mehta and Renza Vento and {Di Fiore}, Riccardo and Richard Ponce-Cusi and Rita Dornetshuber-Fleiss and Rita Nahta and Castellino, {Robert C} and Roberta Palorini and {Abd Hamid}, Roslida and Langie, {Sabine A S} and Eltom, {Sakina E} and Brooks, {Samira A} and Sandra Ryeom and Wise, {Sandra S} and Bay, {Sarah N} and Harris, {Shelley A} and Silvana Papagerakis and Simona Romano and Sofia Pavanello and Staffan Eriksson and Stefano Forte and Casey, {Stephanie C} and Sudjit Luanpitpong and Tae-Jin Lee and Takemi Otsuki and Tao Chen and Thierry Massfelder and Thomas Sanderson and Tiziana Guarnieri and Tove Hultman and Val{\'e}rian Dormoy and Valerie Odero-Marah and Venkata Sabbisetti and Veronique Maguer-Satta and Rathmell, {W Kimryn} and Wilhelm Engstr{\"o}m and Decker, {William K} and Bisson, {William H} and Yon Rojanasakul and Yunus Luqmani and Zhenbang Chen and Zhiwei Hu",
note = "Publisher Copyright: {\textcopyright} The Author 2015.",
year = "2015",
month = jun,
doi = "10.1093/carcin/bgv039",
language = "English",
volume = "36 ",
pages = "S254--S296",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "OXFORD UNIV PRESS",
number = "Suppl 1",
}
Goodson, WH, Lowe, L, Carpenter, DO, Gilbertson, M, Manaf Ali, A, Lopez de Cerain Salsamendi, A, Lasfar, A, Carnero, A, Azqueta, A, Amedei, A, Charles, AK, Collins, AR, Ward, A, Salzberg, AC, Colacci, A, Olsen, A-K, Berg, A, Barclay, BJ, Zhou, BP, Blanco-Aparicio, C, Baglole, CJ, Dong, C, Mondello, C, Hsu, C-W, Naus, CC, Yedjou, C, Curran, CS, Laird, DW, Koch, DC, Carlin, DJ, Felsher, DW, Roy, D, Brown, DG, Ratovitski, E, Ryan, EP, Corsini, E, Rojas, E, Moon, E-Y, Laconi, E, Marongiu, F, Al-Mulla, F, Chiaradonna, F, Darroudi, F, Martin, FL, Van Schooten, FJ, Goldberg, GS, Wagemaker, G, Nangami, GN, Calaf, GM, Williams, G, Wolf, GT, Koppen, G, Brunborg, G, Lyerly, HK, Krishnan, H, Ab Hamid, H, Yasaei, H, Sone, H, Kondoh, H, Salem, HK, Hsu, H-Y, Park, HH, Koturbash, I, Miousse, IR, Scovassi, AI, Klaunig, JE, Vondráček, J, Raju, J, Roman, J, Wise, JP, Whitfield, JR, Woodrick, J, Christopher, JA, Ochieng, J, Martinez-Leal, JF, Weisz, J, Kravchenko, J, Sun, J, Prudhomme, KR, Narayanan, KB, Cohen-Solal, KA, Moorwood, K, Gonzalez, L, Soucek, L, Jian, L, D'Abronzo, LS, Lin, L-T, Li, L, Gulliver, L, McCawley, LJ, Memeo, L, Vermeulen, L, Leyns, L, Zhang, L, Valverde, M, Khatami, M, Romano, MF, Chapellier, M, Williams, MA, Wade, M, Manjili, MH, Lleonart, ME, Xia, M, Gonzalez, MJ, Karamouzis, MV, Kirsch-Volders, M, Vaccari, M, Kuemmerle, NB, Singh, N, Cruickshanks, N, Kleinstreuer, N, van Larebeke, N, Ahmed, N, Ogunkua, O, Krishnakumar, PK, Vadgama, P, Marignani, PA, Ghosh, PM, Ostrosky-Wegman, P, Thompson, PA, Dent, P, Heneberg, P, Darbre, P, Sing Leung, P, Nangia-Makker, P, Cheng, QS, Robey, RB, Al-Temaimi, R, Roy, R, Andrade-Vieira, R, Sinha, RK, Mehta, R, Vento, R, Di Fiore, R, Ponce-Cusi, R, Dornetshuber-Fleiss, R, Nahta, R, Castellino, RC, Palorini, R, Abd Hamid, R, Langie, SAS, Eltom, SE, Brooks, SA, Ryeom, S, Wise, SS, Bay, SN, Harris, SA, Papagerakis, S, Romano, S, Pavanello, S, Eriksson, S, Forte, S, Casey, SC, Luanpitpong, S, Lee, T-J, Otsuki, T, Chen, T, Massfelder, T, Sanderson, T, Guarnieri, T, Hultman, T, Dormoy, V, Odero-Marah, V, Sabbisetti, V, Maguer-Satta, V, Rathmell, WK, Engström, W, Decker, WK, Bisson, WH, Rojanasakul, Y, Luqmani, Y, Chen, Z & Hu, Z 2015, 'Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead', Carcinogenesis, Jg. 36 , Nr. Suppl 1, S. S254-S296. https://doi.org/10.1093/carcin/bgv039
Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment : the challenge ahead. / Goodson, William H (Korresp. Autor*in); Lowe, Leroy; Carpenter, David O et al.
in: Carcinogenesis, Band 36 , Nr. Suppl 1, 06.2015, S. S254-S296.
Veröffentlichungen: Beitrag in Fachzeitschrift › Artikel › Peer Reviewed
TY - JOUR
T1 - Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment
T2 - the challenge ahead
AU - Goodson, William H
AU - Lowe, Leroy
AU - Carpenter, David O
AU - Gilbertson, Michael
AU - Manaf Ali, Abdul
AU - Lopez de Cerain Salsamendi, Adela
AU - Lasfar, Ahmed
AU - Carnero, Amancio
AU - Azqueta, Amaya
AU - Amedei, Amedeo
AU - Charles, Amelia K
AU - Collins, Andrew R
AU - Ward, Andrew
AU - Salzberg, Anna C
AU - Colacci, Annamaria
AU - Olsen, Ann-Karin
AU - Berg, Arthur
AU - Barclay, Barry J
AU - Zhou, Binhua P
AU - Blanco-Aparicio, Carmen
AU - Baglole, Carolyn J
AU - Dong, Chenfang
AU - Mondello, Chiara
AU - Hsu, Chia-Wen
AU - Naus, Christian C
AU - Yedjou, Clement
AU - Curran, Colleen S
AU - Laird, Dale W
AU - Koch, Daniel C
AU - Carlin, Danielle J
AU - Felsher, Dean W
AU - Roy, Debasish
AU - Brown, Dustin G
AU - Ratovitski, Edward
AU - Ryan, Elizabeth P
AU - Corsini, Emanuela
AU - Rojas, Emilio
AU - Moon, Eun-Yi
AU - Laconi, Ezio
AU - Marongiu, Fabio
AU - Al-Mulla, Fahd
AU - Chiaradonna, Ferdinando
AU - Darroudi, Firouz
AU - Martin, Francis L
AU - Van Schooten, Frederik J
AU - Goldberg, Gary S
AU - Wagemaker, Gerard
AU - Nangami, Gladys N
AU - Calaf, Gloria M
AU - Williams, Graeme
AU - Wolf, Gregory T
AU - Koppen, Gudrun
AU - Brunborg, Gunnar
AU - Lyerly, H Kim
AU - Krishnan, Harini
AU - Ab Hamid, Hasiah
AU - Yasaei, Hemad
AU - Sone, Hideko
AU - Kondoh, Hiroshi
AU - Salem, Hosni K
AU - Hsu, Hsue-Yin
AU - Park, Hyun Ho
AU - Koturbash, Igor
AU - Miousse, Isabelle R
AU - Scovassi, A Ivana
AU - Klaunig, James E
AU - Vondráček, Jan
AU - Raju, Jayadev
AU - Roman, Jesse
AU - Wise, John Pierce
AU - Whitfield, Jonathan R
AU - Woodrick, Jordan
AU - Christopher, Joseph A
AU - Ochieng, Josiah
AU - Martinez-Leal, Juan Fernando
AU - Weisz, Judith
AU - Kravchenko, Julia
AU - Sun, Jun
AU - Prudhomme, Kalan R
AU - Narayanan, Kannan Badri
AU - Cohen-Solal, Karine A
AU - Moorwood, Kim
AU - Gonzalez, Laetitia
AU - Soucek, Laura
AU - Jian, Le
AU - D'Abronzo, Leandro S
AU - Lin, Liang-Tzung
AU - Li, Lin
AU - Gulliver, Linda
AU - McCawley, Lisa J
AU - Memeo, Lorenzo
AU - Vermeulen, Louis
AU - Leyns, Luc
AU - Zhang, Luoping
AU - Valverde, Mahara
AU - Khatami, Mahin
AU - Romano, Maria Fiammetta
AU - Chapellier, Marion
AU - Williams, Marc A
AU - Wade, Mark
AU - Manjili, Masoud H
AU - Lleonart, Matilde E
AU - Xia, Menghang
AU - Gonzalez, Michael J
AU - Karamouzis, Michalis V
AU - Kirsch-Volders, Micheline
AU - Vaccari, Monica
AU - Kuemmerle, Nancy B
AU - Singh, Neetu
AU - Cruickshanks, Nichola
AU - Kleinstreuer, Nicole
AU - van Larebeke, Nik
AU - Ahmed, Nuzhat
AU - Ogunkua, Olugbemiga
AU - Krishnakumar, P K
AU - Vadgama, Pankaj
AU - Marignani, Paola A
AU - Ghosh, Paramita M
AU - Ostrosky-Wegman, Patricia
AU - Thompson, Patricia A
AU - Dent, Paul
AU - Heneberg, Petr
AU - Darbre, Philippa
AU - Sing Leung, Po
AU - Nangia-Makker, Pratima
AU - Cheng, Qiang Shawn
AU - Robey, R Brooks
AU - Al-Temaimi, Rabeah
AU - Roy, Rabindra
AU - Andrade-Vieira, Rafaela
AU - Sinha, Ranjeet K
AU - Mehta, Rekha
AU - Vento, Renza
AU - Di Fiore, Riccardo
AU - Ponce-Cusi, Richard
AU - Dornetshuber-Fleiss, Rita
AU - Nahta, Rita
AU - Castellino, Robert C
AU - Palorini, Roberta
AU - Abd Hamid, Roslida
AU - Langie, Sabine A S
AU - Eltom, Sakina E
AU - Brooks, Samira A
AU - Ryeom, Sandra
AU - Wise, Sandra S
AU - Bay, Sarah N
AU - Harris, Shelley A
AU - Papagerakis, Silvana
AU - Romano, Simona
AU - Pavanello, Sofia
AU - Eriksson, Staffan
AU - Forte, Stefano
AU - Casey, Stephanie C
AU - Luanpitpong, Sudjit
AU - Lee, Tae-Jin
AU - Otsuki, Takemi
AU - Chen, Tao
AU - Massfelder, Thierry
AU - Sanderson, Thomas
AU - Guarnieri, Tiziana
AU - Hultman, Tove
AU - Dormoy, Valérian
AU - Odero-Marah, Valerie
AU - Sabbisetti, Venkata
AU - Maguer-Satta, Veronique
AU - Rathmell, W Kimryn
AU - Engström, Wilhelm
AU - Decker, William K
AU - Bisson, William H
AU - Rojanasakul, Yon
AU - Luqmani, Yunus
AU - Chen, Zhenbang
AU - Hu, Zhiwei
N1 - Publisher Copyright:© The Author 2015.
PY - 2015/6
Y1 - 2015/6
N2 - 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.
AB - 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.
KW - Animals
KW - Carcinogenesis
KW - Carcinogens, Environmental
KW - Environmental Exposure
KW - Hazardous Substances
KW - Humans
KW - Neoplasms
UR - http://www.scopus.com/inward/record.url?scp=84937708474&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgv039
DO - 10.1093/carcin/bgv039
M3 - Article
C2 - 26106142
VL - 36
SP - S254-S296
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
IS - Suppl 1
ER -
Goodson WH, Lowe L, Carpenter DO, Gilbertson M, Manaf Ali A, Lopez de Cerain Salsamendi A et al. Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. Carcinogenesis. 2015 Jun;36 (Suppl 1):S254-S296. doi: 10.1093/carcin/bgv039
