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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | S254-S296 |
| Journal | Carcinogenesis |
| Volume | 36 |
| DOIs | |
| State | Published - Jun 1 2015 |
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ASJC Scopus subject areas
- Cancer Research
Cite this
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; Ali, Abdul Manaf; de Cerain Salsamendi, Adela Lopez; 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; Calaf, Gloria M.; Williams, Graeme; Wolf, Gregory T.; Koppen, Gudrun; Brunborg, Gunnar; Kim Lyerly, H.; Krishnan, Harini; Hamid, Hasiah Ab; Yasaei, Hemad; Sone, Hideko; Kondoh, Hiroshi; Salem, Hosni K.; Hsu, Hsue Yin; Park, Hyun Ho; Koturbash, Igor; Miousse, Isabelle R.; Ivana Scovassi, A.; 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; Xia, Menghang; Gonzalez, 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; Dent, Paul; Heneberg, Petr; Darbre, Philippa; Leung, Po Sing; Nangia-Makker, Pratima; Cheng, Qiang Shawn; Brooks Robey, R.; 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 Abd; Langie, Sabine A S; Eltom, Sakina; 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; Kimryn Rathmell, W.; Engström, Wilhelm; Decker, William K.; Bisson, William H.; Rojanasakul, Yon; Luqmani, Yunus; Chen, Zhenbang; Hu, Zhiwei.
In: Carcinogenesis, Vol. 36, 01.06.2015, p. S254-S296.Research output: Contribution to journal › Article
}
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 - Ali, Abdul Manaf
AU - de Cerain Salsamendi, Adela Lopez
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
AU - Calaf, Gloria M.
AU - Williams, Graeme
AU - Wolf, Gregory T.
AU - Koppen, Gudrun
AU - Brunborg, Gunnar
AU - Kim Lyerly, H.
AU - Krishnan, Harini
AU - Hamid, Hasiah Ab
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 - Ivana Scovassi, A.
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
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
AU - Dent, Paul
AU - Heneberg, Petr
AU - Darbre, Philippa
AU - Leung, Po Sing
AU - Nangia-Makker, Pratima
AU - Cheng, Qiang Shawn
AU - Brooks Robey, R.
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 - Hamid, Roslida Abd
AU - Langie, Sabine A S
AU - Eltom, Sakina
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 - Kimryn Rathmell, W.
AU - Engström, Wilhelm
AU - Decker, William K.
AU - Bisson, William H.
AU - Rojanasakul, Yon
AU - Luqmani, Yunus
AU - Chen, Zhenbang
AU - Hu, Zhiwei
PY - 2015/6/1
Y1 - 2015/6/1
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.
UR - http://www.scopus.com/inward/record.url?scp=84937708474&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937708474&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgv039
DO - 10.1093/carcin/bgv039
M3 - Article
VL - 36
SP - S254-S296
JO - Carcinogenesis
JF - Carcinogenesis
SN - 0143-3334
ER -