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Environmental Factor, July 2015

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Exposure to low levels of chemical mixtures linked with cancer

By Sara Mishamandani

Danielle Carlin

Carlin is one of the leads on mixtures research at NIEHS, which focuses on better understanding how combined environmental exposures affect disease progression. (Photo courtesy of Steve McCaw)

Chemicals can sometimes act together to cause cancer, even when low-level exposures to the individual chemicals might not be cancer-causing, or carcinogenic. This important finding emerged from an international task force of more than 170 cancer scientists, known as the Halifax Project, who collaboratively assessed the carcinogenic potential of low-dose exposures to chemical mixtures in the environment.

The Halifax Project task force published a paper in a special issue of the journal Carcinogenesis explaining their review of the key biological pathways and mechanisms related to the formation of cancer. "The Halifax Project was about getting cancer biologists to talk about the specific hallmarks of cancer that they research and the environmental exposures that contribute to those hallmarks," said Danielle Carlin, Ph.D., NIEHS Superfund Research Program (SRP) health scientist administrator. Carlin was part of the task force and a co-author of the review paper.

"The researchers focused on chemicals that don’t get a lot of attention in cancer research because we don’t normally consider them carcinogens by themselves,” she said. “However, mixtures of these chemicals may contribute to cancer.”

NIEHS-funded workshop moves collaboration forward

The review stemmed from a Halifax Project workshop August 8-9, 2013 in Nova Scotia, Canada. "SRP is interested in the NIEHS Strategic Plan goal of understanding how combined environmental exposures affect disease pathogenesis," Carlin said. "This meeting was funded by SRP to foster collaboration and work toward a better understanding of how the joint action of multiple chemical exposures may cause cancer."

Before the meeting, eleven teams of experts were formed to focus on specific mechanistic contributors, or hallmarks, to cancer. Each team identified environmental exposures known to disrupt their particular hallmark. After the meeting, each group prepared a paper on their findings, which were published in a special issue of Carcinogenesis. The collection addressed hallmarks such as tissue invasion and metastasis, evading growth suppression, the tumor microenvironment, and genome instability.

For the recently published article, the expert teams selected 85 chemicals to which the population is routinely exposed. The authors reported that 50 of them may disrupt cancer-related biological mechanisms at low doses.

Reviewing the challenges ahead

“We are definitely concerned that we are now starting to see evidence of a wide range of low-dose effects that are directly related to carcinogenesis, exerted by chemicals that are unavoidable in the environment,” said lead author William Goodson III, M.D., senior scientist at the California Pacific Medical Center in San Francisco.

“This is an area that merits considerable attention, and where interdisciplinary and international collaboration is needed,” said contributing author David Carpenter, Ph.D., director of the Institute for Health and the Environment at the University of Albany in New York. “Although we know a lot about the individual effects of chemicals, we know very little about the combined and additive effects of the many chemicals that we encounter every day in the air, in our water, and in our food.”

In addition to participating in the working groups during the meeting, Carlin gave a presentation on NIEHS priorities and described how NIEHS-funded researchers are working to unravel the health effects of environmental mixtures. Rick Woychik, Ph.D., NIEHS deputy director, gave the keynote on strategic directions in environmental health, and National Toxicology Program toxicologist Cynthia Rider, Ph.D., gave a presentation addressing experimental designs and approaches to studying mixtures, and the importance of studying environmental chemicals as contributors to the onset of cancer.

(Sara Mishamandani is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)

Citation: Goodson WH 3rd, 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 G, Calaf GM, Williams G, Wolf GT, Koppen G, Brunborg G, Kim Lyerly H, 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, Vondráček J, Raju J, Roman J, Wise JP Sr, 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, 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 SA, 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, 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 36(Suppl 1):S254–S296.


participants at the Halifax Project workshop

Participants from around the world used the Halifax Project workshop to collaborate and generate recommendations for advancing mixtures research related to cancer. (Photo courtesy of Danielle Carlin)




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