Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations.
BACKGROUND: The current single-chemical-as-carcinogen risk assessment paradigm might underestimate or miss the cumulative effects of exposure to chemical mixtures, as highlighted in recent work from the Halifax Project. This is particularly important for chemical exposures in the low-dose range that...
| Publicado en: | Environmental Health Perspectives Vol. 125; no. 2; pp. 163 - 170 |
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| Autores principales: | , , , , , |
| Formato: | review Journal Article |
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National Institute of Environmental Health Sciences
Feb2017
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=121119346&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 121119346 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00916765 3B5 jtl: Environmental Health Perspectives issn: 00916765 maglogo: N pubinfo: dt: Feb2017 vid: 125 iid: 2 pid: 56539 pub: National Institute of Environmental Health Sciences place: Research Triangle Park, North Carolina artinfo: ui: 121119346 121119346 121119346 10.1289/EHP411 121119346 ppf: 163 ppct: 7 formats: tig: atl: Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations. aug: au: Miller, Mark F. Goodson III, William H. Manjili, Masoud H. Kleinstreuer, Nicole Bisson, William H. Lowe, Leroy affil: National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA sug: subj: Carcinogens, Environmental Neoplasms Risk Factors Environmental Exposure Research Priorities Seminars and Workshops Environmental Health Policy Making Risk Assessment United States Neoplasms Prevention and Control Toxicology Neoplasms Pathology Models, Biological Tumor Markers, Biological Genetics Research Methodology Neoplasms Immunology Epigenomics ab: BACKGROUND: The current single-chemical-as-carcinogen risk assessment paradigm might underestimate or miss the cumulative effects of exposure to chemical mixtures, as highlighted in recent work from the Halifax Project. This is particularly important for chemical exposures in the low-dose range that may be affecting crucial cancer hallmark mechanisms that serve to enable carcinogenesis. OBJECTIVE: Could ongoing low-dose exposures to a mixture of commonly encountered environmental chemicals produce effects in concert that lead to carcinogenesis? A workshop held at the NIEHS in August 2015 evaluated the scientific support for the low-dose mixture hypothesis of carcinogenesis and developed a research agenda. Here we describe the science that supports this novel theory, identify knowledge gaps, recommend future methodologies, and explore preventative risk assessment and policy decision-making that incorporates cancer biology, environmental health science, translational toxicology, and clinical epidemiology. DISCUSSION AND CONCLUSIONS: The theoretical merits of the low-dose carcinogenesis hypothesis are well founded with clear biological relevance, and therefore, the premise warrants further investigation. Expert recommendations include the need for better insights into the ways in which noncarcinogenic constituents might combine to uniquely affect the process of cellular transformation (in vitro) and environmental carcinogenesis (in vivo), including investigations of the role of key defense mechanisms in maintaining transformed cells in a dormant state. The scientific community will need to acknowledge limitations of animal-based models in predicting human responses; evaluate biological events leading to carcinogenesis both spatially and temporally; examine the overlap between measurable cancer hallmarks and characteristics of carcinogens; incorporate epigenetic biomarkers, in silico modelling, high-performance computing and high-resolution imaging, microbiome, metabolomics, and transcriptomics into future research efforts; and build molecular annotations of network perturbations. The restructuring of many existing regulatory frameworks will require adequate testing of relevant environmental mixtures to build a critical mass of evidence on which to base policy decisions. CITATION: Miller MF, Goodson WH III, Manjili MH, Kleinstreuer N, Bisson WH, Lowe L. 2017. Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: scientific underpinnings and research recommendations. Environ Health Perspect 125:163-169; http://dx.doi.org/10.1289/EHP411 pubtype: Academic Journal doctype: review Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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