Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1289/EHP411 |
Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations | |
Miller, Mark F.1; Goodson, William H., III2; Manjili, Masoud H.3; Kleinstreuer, Nicole1; Bisson, William H.4; Lowe, Leroy5,6 | |
2017-02-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES
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ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2017 |
卷号 | 125期号:2 |
文章类型 | Review |
语种 | 英语 |
国家 | USA; Canada; England |
英文摘要 | 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. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000394004000008 |
WOS关键词 | CANCER HALLMARK ; ENVIRONMENTAL CHEMICALS ; MECHANISMS ; EXPOSURES ; DISRUPTORS ; EVASION ; RISK |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/22393 |
专题 | 资源环境科学 |
作者单位 | 1.NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA; 2.Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA; 3.Virginia Commonwealth Univ, Massey Canc Ctr, Dept Microbiol & Immunol, Richmond, VA USA; 4.Oregon State Univ, Environm & Mol Toxicol, Corvallis, OR 97331 USA; 5.Getting Know Canc, Truro, NS, Canada; 6.Univ Lancaster, Lancaster Environm Ctr, Lancaster, England |
推荐引用方式 GB/T 7714 | Miller, Mark F.,Goodson, William H., III,Manjili, Masoud H.,et al. Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2017,125(2). |
APA | Miller, Mark F.,Goodson, William H., III,Manjili, Masoud H.,Kleinstreuer, Nicole,Bisson, William H.,&Lowe, Leroy.(2017).Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations.ENVIRONMENTAL HEALTH PERSPECTIVES,125(2). |
MLA | Miller, Mark F.,et al."Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations".ENVIRONMENTAL HEALTH PERSPECTIVES 125.2(2017). |
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