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Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis

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Title Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis
Names Hu, Zhiwei (creator)
Brooks, Samira A. (creator)
Dormoy, Valérian (creator)
Bisson, William H. (creator)
et al. (creator)
Date Issued 2015-06 (iso8601)
Note This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Oxford University Press. The published article can be found at: http://carcin.oxfordjournals.org/
Abstract One of the important ‘hallmarks’ of cancer is angiogenesis, which is the process of formation of new blood vessels that
are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well
balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor
microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue
factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to
tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote
tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in
relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity
and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals
with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening
assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of
important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research.
Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach
to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic
mixtures of chemicals with carcinogenic potential.
Genre Article
Identifier Hu, Z., Brooks, S. A., Dormoy, V., Hsu, C. W., Hsu, H. Y., Lin, L. T., ... & Kleinstreuer, N. (2015). Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis. Carcinogenesis, 36(Suppl 1), S184-S202. doi:10.1093/carcin/bgv036

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