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

W.H., 3rd Goodson; L. Lowe; D.O. Carpenter; M. Gilbertson; A. Manaf Ali; A. Lopez de Cerain Salsamendi; A. Lasfar; A. Carnero; A. Azqueta; A. Amedei; A.K. Charles; A.R. Collins; A. Ward; A.C. Salzberg; A. Colacci; A.K. Olsen; A. Berg; B.J. Barclay; B.P. Zhou; C. Blanco-Aparicio; C.J. Baglole; C. Dong; C. Mondello; C.W. Hsu; C.C. Naus; C. Yedjou; C.S. Curran; D.W. Laird; D.C. Koch; D.J. Carlin; D.W. Felsher; D. Roy; D.G. Brown; E. Ratovitski; E.P. Ryan; E. Corsini; E. Rojas; E.Y. Moon; E. Laconi; F. Marongiu; F. Al-Mulla; F. Chiaradonna; F. Darroudi; F.L. Martin; F.J. van Schooten; G.S. Goldberg; G. Wagemaker; G.N. Nangami; G.M. Calaf; G. Williams; G.T. Wolf; G. Koppen; G. Brunborg; H.K. Lyerly; H. Krishnan; H. Ab Hamid; H. Yasaei; H. Sone; H. Kondoh; H.K. Salem; H.Y. Hsu; H.H. Park; I. Koturbash; I.R. Miousse; A.I. Scovassi; J.E. Klaunig; J. Vondracek; J. Raju; J. Roman; J.P., Sr. Wise; J.R. Whitfield; J. Woodrick; J.A. Christopher; J. Ochieng; J.F. Martinez-Leal; J. Weisz; J. Kravchenko; J. Sun; K.R. Prudhomme; K.B. Narayanan; K.A. Cohen-Solal; K. Moorwood; L. Gonzalez; L. Soucek; L. Jian; L.S. D'Abronzo; L.T. Lin; L. Li; L. Gulliver; L.J. McCawley; L. Memeo; L. Vermeulen; L. Leyns; L. Zhang; M. Valverde; M. Khatami; M.F Romano; M. Chapellier; M.A. Williams; M., et al. Wade

doi:10.1093/carcin/bgv039

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

W.H., 3rd Goodson^*, L. Lowe, D.O. Carpenter, M. Gilbertson, A. Manaf Ali, A. Lopez de Cerain Salsamendi, A. Lasfar, A. Carnero, A. Azqueta, A. Amedei, A.K. Charles, A.R. Collins, A. Ward, A.C. Salzberg, A. Colacci, A.K. Olsen, A. Berg, B.J. Barclay, B.P. Zhou, C. Blanco-AparicioC.J. Baglole, C. Dong, C. Mondello, C.W. Hsu, C.C. Naus, C. Yedjou, C.S. Curran, D.W. Laird, D.C. Koch, D.J. Carlin, D.W. Felsher, D. Roy, D.G. Brown, E. Ratovitski, E.P. Ryan, E. Corsini, E. Rojas, E.Y. Moon, E. Laconi, F. Marongiu, F. Al-Mulla, F. Chiaradonna, F. Darroudi, F.L. Martin, F.J. van Schooten, G.S. Goldberg, G. Wagemaker, G.N. Nangami, G.M. Calaf, G. Williams, G.T. Wolf, G. Koppen, G. Brunborg, H.K. Lyerly, H. Krishnan, H. Ab Hamid, H. Yasaei, H. Sone, H. Kondoh, H.K. Salem, H.Y. Hsu, H.H. Park, I. Koturbash, I.R. Miousse, A.I. Scovassi, J.E. Klaunig, J. Vondracek, J. Raju, J. Roman, J.P., Sr. Wise, J.R. Whitfield, J. Woodrick, J.A. Christopher, J. Ochieng, J.F. Martinez-Leal, J. Weisz, J. Kravchenko, J. Sun, K.R. Prudhomme, K.B. Narayanan, K.A. Cohen-Solal, K. Moorwood, L. Gonzalez, L. Soucek, L. Jian, L.S. D'Abronzo, L.T. Lin, L. Li, L. Gulliver, L.J. McCawley, L. Memeo, L. Vermeulen, L. Leyns, L. Zhang, M. Valverde, M. Khatami, M.F Romano, M. Chapellier, M.A. Williams, M., et al. Wade

^*Corresponding author for this work

Farmacologie en Toxicologie

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

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
Pages (from-to)	S254-S296
Number of pages	43
Journal	Carcinogenesis
Volume	36 Suppl 1
DOIs	https://doi.org/10.1093/carcin/bgv039
Publication status	Published - Jun 2015

Keywords

EPITHELIAL-MESENCHYMAL TRANSITION
ESTROGEN-RECEPTOR-ALPHA
BREAST-CANCER CELLS
ACTIVATED PROTEIN-KINASES
POLYBROMINATED DIPHENYL ETHERS
ENDOCRINE-DISRUPTING CHEMICALS
VASCULAR ENDOTHELIAL-CELLS
METHOXYCHLOR-INDUCED ALTERATIONS
MIGRATION INHIBITORY FACTOR
TARGETING TISSUE FACTOR

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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., ... Wade, M. . E. A. (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

@article{35c2cbf637314e4c8c1db506dd60b00c,

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 = "EPITHELIAL-MESENCHYMAL TRANSITION, ESTROGEN-RECEPTOR-ALPHA, BREAST-CANCER CELLS, ACTIVATED PROTEIN-KINASES, POLYBROMINATED DIPHENYL ETHERS, ENDOCRINE-DISRUPTING CHEMICALS, VASCULAR ENDOTHELIAL-CELLS, METHOXYCHLOR-INDUCED ALTERATIONS, MIGRATION INHIBITORY FACTOR, TARGETING TISSUE FACTOR",

author = "Goodson, {W.H., 3rd} and L. Lowe and D.O. Carpenter and M. Gilbertson and {Manaf Ali}, A. and {Lopez de Cerain Salsamendi}, A. and A. Lasfar and A. Carnero and A. Azqueta and A. Amedei and A.K. Charles and A.R. Collins and A. Ward and A.C. Salzberg and A. Colacci and A.K. Olsen and A. Berg and B.J. Barclay and B.P. Zhou and C. Blanco-Aparicio and C.J. Baglole and C. Dong and C. Mondello and C.W. Hsu and C.C. Naus and C. Yedjou and C.S. Curran and D.W. Laird and D.C. Koch and D.J. Carlin and D.W. Felsher and D. Roy and D.G. Brown and E. Ratovitski and E.P. Ryan and E. Corsini and E. Rojas and E.Y. Moon and E. Laconi and F. Marongiu and F. Al-Mulla and F. Chiaradonna and F. Darroudi and F.L. Martin and {van Schooten}, F.J. and G.S. Goldberg and G. Wagemaker and G.N. Nangami and G.M. Calaf and G. Williams and G.T. Wolf and G. Koppen and G. Brunborg and H.K. Lyerly and H. Krishnan and {Ab Hamid}, H. and H. Yasaei and H. Sone and H. Kondoh and H.K. Salem and H.Y. Hsu and H.H. Park and I. Koturbash and I.R. Miousse and A.I. Scovassi and J.E. Klaunig and J. Vondracek and J. Raju and J. Roman and Wise, {J.P., Sr.} and J.R. Whitfield and J. Woodrick and J.A. Christopher and J. Ochieng and J.F. Martinez-Leal and J. Weisz and J. Kravchenko and J. Sun and K.R. Prudhomme and K.B. Narayanan and K.A. Cohen-Solal and K. Moorwood and L. Gonzalez and L. Soucek and L. Jian and L.S. D'Abronzo and L.T. Lin and L. Li and L. Gulliver and L.J. McCawley and L. Memeo and L. Vermeulen and L. Leyns and L. Zhang and M. Valverde and M. Khatami and M.F Romano and M. Chapellier and M.A. Williams and Wade, {M., et al.}",

year = "2015",

month = jun,

doi = "10.1093/carcin/bgv039",

language = "English",

volume = "36 Suppl 1",

pages = "S254--S296",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

}

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, 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, 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, HY, Park, HH, Koturbash, I, Miousse, IR, Scovassi, AI, Klaunig, JE, Vondracek, J, Raju, J, Roman, J, Wise, JPS, 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, MEA 2015, 'Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead', Carcinogenesis, vol. 36 Suppl 1, pp. S254-S296. https://doi.org/10.1093/carcin/bgv039

TY - JOUR

T1 - Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead

AU - Goodson, W.H., 3rd

AU - Lowe, L.

AU - Carpenter, D.O.

AU - Gilbertson, M.

AU - Manaf Ali, A.

AU - Lopez de Cerain Salsamendi, A.

AU - Lasfar, A.

AU - Carnero, A.

AU - Azqueta, A.

AU - Amedei, A.

AU - Charles, A.K.

AU - Collins, A.R.

AU - Ward, A.

AU - Salzberg, A.C.

AU - Colacci, A.

AU - Olsen, A.K.

AU - Berg, A.

AU - Barclay, B.J.

AU - Zhou, B.P.

AU - Blanco-Aparicio, C.

AU - Baglole, C.J.

AU - Dong, C.

AU - Mondello, C.

AU - Hsu, C.W.

AU - Naus, C.C.

AU - Yedjou, C.

AU - Curran, C.S.

AU - Laird, D.W.

AU - Koch, D.C.

AU - Carlin, D.J.

AU - Felsher, D.W.

AU - Roy, D.

AU - Brown, D.G.

AU - Ratovitski, E.

AU - Ryan, E.P.

AU - Corsini, E.

AU - Rojas, E.

AU - Moon, E.Y.

AU - Laconi, E.

AU - Marongiu, F.

AU - Al-Mulla, F.

AU - Chiaradonna, F.

AU - Darroudi, F.

AU - Martin, F.L.

AU - van Schooten, F.J.

AU - Goldberg, G.S.

AU - Wagemaker, G.

AU - Nangami, G.N.

AU - Calaf, G.M.

AU - Williams, G.

AU - Wolf, G.T.

AU - Koppen, G.

AU - Brunborg, G.

AU - Lyerly, H.K.

AU - Krishnan, H.

AU - Ab Hamid, H.

AU - Yasaei, H.

AU - Sone, H.

AU - Kondoh, H.

AU - Salem, H.K.

AU - Hsu, H.Y.

AU - Park, H.H.

AU - Koturbash, I.

AU - Miousse, I.R.

AU - Scovassi, A.I.

AU - Klaunig, J.E.

AU - Vondracek, J.

AU - Raju, J.

AU - Roman, J.

AU - Wise, J.P., Sr.

AU - Whitfield, J.R.

AU - Woodrick, J.

AU - Christopher, J.A.

AU - Ochieng, J.

AU - Martinez-Leal, J.F.

AU - Weisz, J.

AU - Kravchenko, J.

AU - Sun, J.

AU - Prudhomme, K.R.

AU - Narayanan, K.B.

AU - Cohen-Solal, K.A.

AU - Moorwood, K.

AU - Gonzalez, L.

AU - Soucek, L.

AU - Jian, L.

AU - D'Abronzo, L.S.

AU - Lin, L.T.

AU - Li, L.

AU - Gulliver, L.

AU - McCawley, L.J.

AU - Memeo, L.

AU - Vermeulen, L.

AU - Leyns, L.

AU - Zhang, L.

AU - Valverde, M.

AU - Khatami, M.

AU - Romano, M.F

AU - Chapellier, M.

AU - Williams, M.A.

AU - Wade, M., et al.

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 - EPITHELIAL-MESENCHYMAL TRANSITION

KW - ESTROGEN-RECEPTOR-ALPHA

KW - BREAST-CANCER CELLS

KW - ACTIVATED PROTEIN-KINASES

KW - POLYBROMINATED DIPHENYL ETHERS

KW - ENDOCRINE-DISRUPTING CHEMICALS

KW - VASCULAR ENDOTHELIAL-CELLS

KW - METHOXYCHLOR-INDUCED ALTERATIONS

KW - MIGRATION INHIBITORY FACTOR

KW - TARGETING TISSUE FACTOR

U2 - 10.1093/carcin/bgv039

DO - 10.1093/carcin/bgv039

M3 - Article

C2 - 26106142

SN - 0143-3334

VL - 36 Suppl 1

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

Abstract

Keywords

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