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; Salsamendi, Adela Lopez de Cerain; Lasfar, Ahmed; Carnero, Amancio; Azqueta, Amaya; Amedei, Amedeo; Charles, Amelia K; Collins, Andrew; Ward, Andrew; Salzberg, Anna C.; Colacci, Annamaria; Olsen, Ann‐Karin; Berg, Arthur; Barclay, B. J.; Zhou, Binhua P.; Blanco‐Aparicio, Carmen; Baglole, Carolyn J.; Dong, Chenfang; Mondello, Chiara; Hsu, Chia-Wen; Naus, Christian C.; Yedjou, Clément G.; Curran, Colleen S.; Laird, Dale W.; Koch, Daniel C.; Carlin, Danielle J.; Felsher, Dean W.; Roy, Debasish; Brown, Dustin G.; Ratovitski, Edward A.; Ryan, Elizabeth P.; Corsini, Emanuela; Rojas, Emilio; Moon, Eun‐Yi; Laconi, Ezio; Marongiu, Fabio; Al-Mulla, Fahd; Chiaradonna, Ferdinando; Darroudi, F.; Martin, Francis L.; Schooten, Frederik J. van; Goldberg, Gary S.; Wagemaker, Gerard; Nangami, Gladys N.; Calaf, Gloria M.; Williams, Graeme; Wolf, Gregory T.; Koppen, Gudrun; Brunborg, Gunnar; Lyerly, H. Kim; Krishnan, Harini; Hamid, Hasiah Ab; Yasaei, Hemad; Sone, Hirohito; Kondoh, Hiroshi; Salem, Hosni; Hsu, Hsue-Yin; Park, Hyun Ho; Koturbash, Igor; Miousse, Isabelle R.; Scovassi, Anna Ivana; Klaunig, James E.; Vondráček, Jan; Raju, Jayadev; Roman, Jesse; Wise, John Pierce; Whitfield, Jonathan R.; Woodrick, Jordan; Christopher, Joseph; Ochieng, Josiah; Martínez-Leal, Juan Fernando; Weisz, Judith; Kravchenko, Julia; Sun, Jun; Prudhomme, Kalan R.; Narayanan, Kannan Badri; Cohen‐Solal, Karine; 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; Chapellier, Marion; Williams, Marc A.; Wade, Mark; Manjili, Masoud H.; Lleonart, Matilde E.; Xia, Menghang; González, Michael J.; Karamouzis, Michalis V.; Kirsch‐Volders, Micheline; Vaccari, Monica; Kuemmerle, Nancy B.; Singh, Neetu; Cruickshanks, Nichola; Kleinstreuer, Nicole; Larebeke, Nik van; Ahmed, Nuzhat; Ogunkua, Olugbemiga; Krishnakumar, P. K.; Vadgama, Pankaj; Marignani, Paola A.; Ghosh, Paramita M.; Ostrosky‐Wegman, Patricia; Thompson, Patricia A.; Dent, Paul; Heneberg, Petr; Darbre, Philippa D.; Leung, Po Sing; Nangia‐Makker, Pratima; Cheng, Qiang; Robey, R. Brooks; Al-Temaimi, Rabeah; Roy, Rabindra; Andrade-Vieira, Rafaela; Sinha, Ranjeet Kumar; Mehta, Rekha; Vento, Renza; Fiore, Riccardo Di; Ponce‐Cusi, Richard; Dornetshuber-Fleiss, Rita; Nahta, Rita; Castellino, Robert C.; Palorini, Roberta; Hamid, Roslida Abdul; Langie, Sabine A. S.; Eltom, Sakina E.; 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, J. Thomas; Guarnieri, Tiziana; Hultman, Tove; Dormoy, Valérian; Odero-Marah, Valerie; Sabbisetti, Venkata; Maguer-Satta, Véronique; Rathmell, W. Kimryn; Engström, Wilhelm; Decker, William K.; Bisson, William H.; Rojanasakul, Yon; Luqmani, Yunus A.; Chen, Zhenbang; Hu, Zhiwei

doi:10.1093/carcin/bgv039

Cited by 259 publications

(177 citation statements)

References 460 publications

(315 reference statements)

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“…Fourteen characteristics relevant to carcinogenesis and breast cancer development identified from seminal papers formed the biological foundation for the BCScreen gene list [21,19,43,48]. These characteristics were each matched to one or more MeSH terms, and linked to a multi-source gene-MeSH association network.…”

Section: Discussionmentioning

confidence: 99%

“…To capture key biological characteristics important in breast carcinogenesis, we identified seminal papers on carcinogenesis [21,19,48] and breast cancer [43]. Reviewing these articles, we compiled 14 common characteristics or biological processes important in breast carcinogenesis (Table 1).…”

Section: Rg Grashow Et Almentioning

confidence: 99%

“…Genes with highest summary score Percentage of genes appearing on S1500+ [16][17][18][19][20][21][22][23][24] Enrichment analysis of BCScreen identifies key characteristics of breast carcinogenesis Fig. 4 shows the top five significant pathways and terms from nine libraries which include WikiPathways, Reactome, Protein ANalysis THrough Evolutionary Relationships (PANTHER), Disease_perturbations_from_GEO_down (GEO), OMIM_Disease (OMIM), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) Biological Process, Human Metabolome Database (HMDB), and the Nuclear Receptor Signaling Atlas (NURSA).…”

Section: Characteristicmentioning

confidence: 99%

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BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening

Grashow

Rosa

Watford

et al. 2018

Computational Toxicology

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A B S T R A C TTargeted gene lists have been used in clinical settings to specify breast tumor type, and to predict breast cancer prognosis and response to treatment. Separately, panels have been curated to predict systemic toxicity and xenoestrogen activity as a part of chemical screening strategies. However, currently available panels do not specifically target biological processes relevant to breast development and carcinogenesis. We have developed a gene panel called the Breast Carcinogen Screen (BCScreen) as a tool to identify potential breast carcinogens and characterize mechanisms of toxicity. First, we used four seminal reviews to identify 14 key characteristics of breast carcinogenesis, such as apoptosis, immunomodulation, and genotoxicity. Then, using a hybrid data and knowledge-driven framework, we systematically combined information from whole transcriptome data from genomic databases, biomedical literature, the CTD chemical-gene interaction database, and primary literature review to generate a panel of 500 genes relevant to breast carcinogenesis. We used normalized pointwise mutual information (NPMI) to rank genes that frequently co-occurred with key characteristics in biomedical literature. We found that many genes identified for BCScreen were not included in prognostic breast cancer or systemic toxicity panels. For example, more than half of BCScreen genes were not included in the Tox21 S1500+ general toxicity gene list. Of the 230 that did overlap between the two panels, representation varied across characteristics of carcinogenesis ranging from 21% for genes associated with epigenetics to 82% for genes associated with xenobiotic metabolism. Enrichment analysis of BCScreen identified pathways and processes including response to steroid hormones, cancer, cell cycle, apoptosis, DNA damage and breast cancer. The biologically-based systematic approach to gene prioritization demonstrated here provides a flexible framework for creating diseasefocused gene panels to support discovery related to etiology. With validation, BCScreen may also be useful for toxicological screening relevant to breast carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Rg Grashow Et Almentioning

confidence: 99%

Section: Characteristicmentioning

confidence: 99%

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BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening

Grashow

Rosa

Watford

et al. 2018

Computational Toxicology

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“…Goodson et al, 2015) Both non-genotoxic and genotoxic substances can trigger oxidative stress (Ellinger-Ziegelbauer et al, 2005), see also Table 1, which can also lead to adverse outcomes other than cancer. One of the main pathways related to oxidative stress is orchestrated by p53.…”

Section: What Are Non-genotoxic Carcinogens?mentioning

confidence: 99%

International regulatory needs for development ofan IATA for non-genotoxic carcinogenic chemical substances

Jacobs

Colacci

Louekari³

et al. 2016

ALTEX

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“…Exposure to toxic environmental chemicals contributes to 7-19 % of cancers in humans (Goodson et al 2015). Among the total number of Group 1 agents (known human carcinogens as per IARC classification), most of them belong to different classes of chemicals (Baan et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of interaction and combined toxicity of polyaromatic hydrocarbons (PAHs) and metals using human cell-based bioassays

Muthusamy¹

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Mixed contamination of polyaromatic hydrocarbons (PAHs) and metals are ubiquitous in the environment. Some of the individual PAHs are known as human carcinogens, and metals are associated with various systemic toxicity and cancers in humans. Although the individual toxicity of PAHs and metals are well documented, our present state of knowledge about the adverse health effects of these mixtures is very limited in terms of exposure associated toxicity in humans, the underlying mechanism of toxicity and predicting the toxicity of mixtures. Due to this, their risk assessment has been mostly carried out based on their individual toxicity data.This research work investigated the interaction and combined toxicity of four PAHs

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

Abstract: SummaryLow-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated.

Cited by 259 publications

References 460 publications

BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening

BCScreen: A gene panel to test for breast carcinogenesis in chemical safety screening

International regulatory needs for development ofan IATA for non-genotoxic carcinogenic chemical substances

Evaluation of interaction and combined toxicity of polyaromatic hydrocarbons (PAHs) and metals using human cell-based bioassays

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