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

H.Goodson III, William and Lowe, Leroy and O.Carpenter, David and Gilbertson, Michael and Ali, Abdul Manaf and de Cerain Salsamendi, Adela Lopez and Lasfar, Ahmed and Carnero, Amancio and Azqueta, Amaya and Amedei, Amedeo and K.Charles, Amelia and R.Collins, Andrew and Ward, Andrew and C.Salzberg, Anna and Colacci, Annamaria and Olsen, Ann-Karin and Berg, Arthur and J.Barclay, Barry and P.Zhou, Binhua and Blanco-Aparicio, Carmen and J.Baglole, Carolyn and Dong, Chenfang and Mondello, Chiara and Hsu, Chia-Wen and C.Naus, Christian and Yedjou, Clement and S.Curran, Colleen and W.Laird, Dale and C.Koch, Daniel and J.Carlin, Danielle and W.Felsher, Dean and Roy, Debasish and G.Brown, Dustin and Ratovitski, Edward and P.Ryan, Elizabeth and Corsini, Emanuela and Rojas, Emilio and Moon, Eun-Yi and Laconi, Ezio and Marongiu, Fabio and Al-Mulla, Fahd and Chiaradonna, Ferdinando and Darroudi, Firouz and L.Martin, Francis and J.Van Schooten, Frederik and S.Goldberg, Gary and Wagemaker, Gerard and Nangami, Gladys and M.Calaf, Gloria and Williams, Graeme and T.Wolf, Gregory and Koppen, Gudrun and Brunborg, Gunnar and Lyerly, H.Kim and Krishnan, Harini and Ab Hamid, Hasiah and Yasaei, Hemad and Sone, Hideko and Kondoh, Hiroshi and K.Salem, Hosni and Hsu, Hsue-Yin and Park, Hyun Ho and Koturbash, Igor and R.Miousse, Isabelle and Scovassi, A.Ivana and E.Klaunig, James and Vondráček, Jan and Raju, Jayadev and Roman, Jesse and Pierce Wise Sr., John and R.Whitfield, Jonathan and Woodrick, Jordan and A.Christopher, Joseph and Ochieng, Josiah and Martinez-Leal, Juan Fernando and Weisz, Judith and Kravchenko, Julia and Sun, Jun and R.Prudhomme, Kalan and Narayanan, Kannan Badri and A.Cohen-Solal, Karine and Moorwood, Kim and Gonzalez, Laetitia and Soucek, Laura and Jian, Le and S.D’Abronzo, Leandro and Lin, Liang-Tzung and Li, Lin and Gulliver, Linda and J.McCawley, Lisa and Memeo, Lorenzo and Vermeulen, Louis and Leyns, Luc and Zhang, Luoping and Valverde, Mahara and Khatami, Mahin and Romano, Maria Fiammetta and Chapellier, Marion and A.Williams, Marc and Wade, Mark and H.Manjili, Masoud and Lleonart, Matilde and Xia, Menghang and J.Gonzalez, Michael and V.Karamouzis, Michalis and Kirsch-Volders, Micheline and Vaccari, Monica and B.Kuemmerle, Nancy and Singh, Neetu and Cruickshanks, Nichola and Kleinstreuer, Nicole and van Larebeke, Nik and Ahmed, Nuzhat and Ogunkua, Olugbemiga and Krishnakumar, P.K. and Vadgama, Pankaj and A.Marignani, Paola and M.Ghosh, Paramita and Ostrosky-Wegman, Patricia and Thompson, Patricia and Dent, Paul and Heneberg, Petr and Darbre, Philippa and Leung, Po Sing and Nangia-Makker, Pratima and Cheng, Qiang (Shawn) and Robey, R.Brooks and Al-Temaimi, Rabeah and Roy, Rabindra and Andrade-Vieira, Rafaela and K.Sinha, Ranjeet and Mehta, Rekha and Vento, Renza and Di Fiore, Riccardo and Ponce-Cusi, Richard and Dornetshuber-Fleiss, Rita and Nahta, Rita and C.Castellino, Robert and Palorini, Roberta and Abd Hamid, Roslida and A.S.Langie, Sabine and Eltom, Sakina and A.Brooks, Samira and Ryeom, Sandra and S.Wise, Sandra and N.Bay, Sarah and A.Harris, Shelley and Papagerakis, Silvana and Romano, Simona and Pavanello, Sofia and Eriksson, Staffan and Forte, Stefano and C.Casey, Stephanie and Luanpitpong, Sudjit and Lee, Tae-Jin and Otsuki, Takemi and Chen, Tao and Massfelder, Thierry and Sanderson, Thomas and Guarnieri, Tiziana and Hultman, Tove and Dormoy, Valérian and Odero-Marah, Valerie and Sabbisetti, Venkata and Maguer-Satta, Veronique and Rathmell, W.Kimryn and Engström, Wilhelm and K.Decker, William and H.Bisson, William and Rojanasakul, Yon and Luqmani, Yunus and Chen, Zhenbang (2015) Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead. CARCINOGENESIS, 36 (S1). S254-S296. ISSN 0143-3334 (Printed) 1460-2180 (Online)

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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

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Faculty / Institute: Faculty of Bioresources & Food Industry
Depositing User: Prof Dr Abd Manaf Ali
Date Deposited: 26 Aug 2015 00:39
Last Modified: 26 Aug 2015 00:39

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