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

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

doi:10.1093/carcin/bgv039

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

159 Scopus citations

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	https://doi.org/10.1093/carcin/bgv039
State	Published - Jun 1 2015

ASJC Scopus subject areas

Cancer Research

Access to Document

10.1093/carcin/bgv039

Cite this

Goodson, W. H., Lowe, L., Carpenter, D. O., Gilbertson, M., Ali, A. M., de Cerain Salsamendi, A. L., 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, S254-S296. https://doi.org/10.1093/carcin/bgv039

Goodson, WH, Lowe, L, Carpenter, DO, Gilbertson, M, Ali, AM, de Cerain Salsamendi, AL, Lasfar, A, Carnero, A, Azqueta, A, Amedei, A, Charles, AK, Collins, AR, Ward, A, Salzberg, AC, Colacci, A, Olsen, AK, Berg, A, Barclay, BJ, Zhou, BP, Blanco-Aparicio, C, Baglole, CJ, Dong, C, Mondello, C, Hsu, CW, 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, EY, Laconi, E, Marongiu, F, Al-Mulla, F, Chiaradonna, F, Darroudi, F, Martin, FL, Van Schooten, FJ, Goldberg, GS, Wagemaker, G, Nangami, G, Calaf, GM, Williams, G, Wolf, GT, Koppen, G, Brunborg, G, Kim Lyerly, H, Krishnan, H, Hamid, HA, Yasaei, H, Sone, H, Kondoh, H, Salem, HK, Hsu, HY, Park, HH, Koturbash, I, Miousse, IR, Ivana Scovassi, A, 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, LT, 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, M, 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, P, Dent, P, Heneberg, P, Darbre, P, Leung, PS, Nangia-Makker, P, Cheng, QS, Brooks Robey, R, 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, Hamid, RA, Langie, SAS, Eltom, S, 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, TJ, Otsuki, T, Chen, T, Massfelder, T, Sanderson, T, Guarnieri, T, Hultman, T, Dormoy, V, Odero-Marah, V, Sabbisetti, V, Maguer-Satta, V, Kimryn Rathmell, W, 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, vol. 36, pp. S254-S296. https://doi.org/10.1093/carcin/bgv039

@article{63151cda8e1f4505a7ce68b94a4109ad,

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.",

author = "Goodson, {William H.} and Leroy Lowe and Carpenter, {David O.} and Michael Gilbertson and Ali, {Abdul Manaf} and {de Cerain Salsamendi}, {Adela Lopez} 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 Olsen, {Ann Karin} 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 Hsu, {Chia Wen} 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 Moon, {Eun Yi} 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 Gladys Nangami and Calaf, {Gloria M.} and Graeme Williams and Wolf, {Gregory T.} and Gudrun Koppen and Gunnar Brunborg and {Kim Lyerly}, H. and Harini Krishnan and Hamid, {Hasiah Ab} and Hemad Yasaei and Hideko Sone and Hiroshi Kondoh and Salem, {Hosni K.} and Hsu, {Hsue Yin} and Park, {Hyun Ho} and Igor Koturbash and Miousse, {Isabelle R.} and {Ivana Scovassi}, A. 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 Lin, {Liang Tzung} 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 Matilde Lleonart 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 Patricia Thompson and Paul Dent and Petr Heneberg and Philippa Darbre and Leung, {Po Sing} and Pratima Nangia-Makker and Cheng, {Qiang Shawn} and {Brooks Robey}, R. 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 Hamid, {Roslida Abd} and Langie, {Sabine A S} and Sakina Eltom 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 Lee, {Tae Jin} 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 {Kimryn Rathmell}, W. 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",

year = "2015",

month = jun,

day = "1",

doi = "10.1093/carcin/bgv039",

language = "English (US)",

volume = "36",

pages = "S254--S296",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

}

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

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U2 - 10.1093/carcin/bgv039

DO - 10.1093/carcin/bgv039

M3 - Article

AN - SCOPUS:84937708474

SN - 0143-3334

VL - 36

SP - S254-S296

JO - Carcinogenesis

JF - Carcinogenesis

ER -

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

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