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Title: Identification of potential biomarkers of exposure to diundecyl phthalate

Authors:
; ; ;
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1338624
Resource Type:
Journal Article: Publisher's Accepted Manuscript
Journal Name:
Environmental Research
Additional Journal Information:
Journal Volume: 148; Journal Issue: C; Related Information: CHORUS Timestamp: 2017-10-04 15:04:38; Journal ID: ISSN 0013-9351
Publisher:
Elsevier
Country of Publication:
United States
Language:
English

Citation Formats

Silva, Manori J., Bontke, Trevor W., Calafat, Antonia M., and Ye, Xiaoyun. Identification of potential biomarkers of exposure to diundecyl phthalate. United States: N. p., 2016. Web. doi:10.1016/j.envres.2016.03.037.
Silva, Manori J., Bontke, Trevor W., Calafat, Antonia M., & Ye, Xiaoyun. Identification of potential biomarkers of exposure to diundecyl phthalate. United States. doi:10.1016/j.envres.2016.03.037.
Silva, Manori J., Bontke, Trevor W., Calafat, Antonia M., and Ye, Xiaoyun. 2016. "Identification of potential biomarkers of exposure to diundecyl phthalate". United States. doi:10.1016/j.envres.2016.03.037.
@article{osti_1338624,
title = {Identification of potential biomarkers of exposure to diundecyl phthalate},
author = {Silva, Manori J. and Bontke, Trevor W. and Calafat, Antonia M. and Ye, Xiaoyun},
abstractNote = {},
doi = {10.1016/j.envres.2016.03.037},
journal = {Environmental Research},
number = C,
volume = 148,
place = {United States},
year = 2016,
month = 7
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1016/j.envres.2016.03.037

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  • Phthalates are industrial additives widely used as plasticizers. In addition to deleterious effects on male genital development, population studies have documented correlations between phthalates exposure and impacts on reproductive tract development and on the metabolic syndrome in male adults. In this work we investigated potential mechanisms underlying the impact of DEHP on adult mouse liver in vivo. A parallel analysis of hepatic transcript and metabolic profiles from adult mice exposed to varying DEHP doses was performed. Hepatic genes modulated by DEHP are predominantly PPAR{alpha} targets. However, the induction of prototypic cytochrome P450 genes strongly supports the activation of additional NRmore » pathways, including Constitutive Androstane Receptor (CAR). Integration of transcriptomic and metabonomic profiles revealed a correlation between the impacts of DEHP on genes and metabolites related to heme synthesis and to the Rev-erb{alpha} pathway that senses endogenous heme level. We further confirmed the combined impact of DEHP on the hepatic expression of Alas1, a critical enzyme in heme synthesis and on the expression of Rev-erb{alpha} target genes involved in the cellular clock and in energy metabolism. This work shows that DEHP interferes with hepatic CAR and Rev-erb{alpha} pathways which are both involved in the control of metabolism. The identification of these new hepatic pathways targeted by DEHP could contribute to metabolic and endocrine disruption associated with phthalate exposure. Gene expression profiles performed on microdissected testis territories displayed a differential responsiveness to DEHP. Altogether, this suggests that impacts of DEHP on adult organs, including testis, could be documented and deserve further investigations.« less
  • The radiation chemistry of poly(vinyl chloride) (PVC) blended with trimethylolpropanetrimethacrylate (TMPTMA) and diundecyl phthalate (DUP) has been examined. This three-component mixture contains a base resin (PVC), a crosslinking sensitizer (TMPTMA), and a physical modifier (DUP). These are the basic components in any radiation-curable coating. The kinetics and mechanism of the crosslinking reactions were studied with reference to the dependence on radiation dose and blend composition. The polyfunctional TMPTMA underwent polymerization incorporating the PVC into a 3-dimensional network. DUP remained chemically inert during the irradiation, not being bound to the network. However, DUP by plasticizing the macromolecules and diluting the monomer,more » changed the kinetics extensively. DUP enhanced TMPTMA homopolymerization, TMPTMA grafting, and PVC crosslinking reaction rates. The effect of the competition between polymerization, grafting, and degradation reactions was examined in terms of enhanced mobility of the reacting species. The influence of these kinetics considerations in selecting a blend composition for a coating application was discussed.« less
  • Blends of poly(vinyl chloride)(PVC) with polyfunctional monomers may be crosslinked by ionizing radiation. The physical properties of PVC blended with trimethylolpropanetrimethacrylate (TMPTMA) and diundecyl phthalate (DUP) were studied. The TMPTMA monomer crosslinked the blend by homopolymerization and/or grafting to PVC. The plasticizer, DUP, was chemically inert under irradiation but, by plasticizing the macromolecules and diluting the monomer, changed the kinetics extensively. Characteristics of the glass transitions and the tensile mechanical properties have been correlated with blend composition and radiation dose. Before irradiation, poly(vinyl chloride) was plasticized by both DUP and TMPTMA monomer. The increase in glass transition temperature and mechanicalmore » strength following irradiation to 5 Mrad was correlated with the TMPTMA content of the blend. Both the molecular structure of the network and the DUP content of the blend were factors in determining the physical properties of the final crosslinked blend. The molecular structure was determined by the kinetics of the crosslinking reactions, which in turn were determined by the blend composition. A molecular interpretation consistent with the physical properties, chemical kinetics, and mechanism of the crosslinking system has been presented. 24 figures, 2 tables.« less
  • Purpose: Specific genes expressed as a result of whole body exposure to {gamma}-radiation have been previously identified. In this study, we examined the genes further as possible biomarkers for the blood lymphocytes of C57BL/6 mice after whole body or local irradiation of the thorax, abdomen, and left subphrenic area. Methods and Materials: We performed reverse transcriptase-polymerase chain reaction and real-time reverse transcriptase-polymerase chain reaction analysis of genes encoding platelet membrane glycoprotein IIb, protein tyrosine kinase, sialyltransferase, and Cu/ZnSOD in blood lymphocytes, lung tissue, spleen, and intestines. The protein expression in blood lymphocytes was confirmed by Western blot analysis. Results: Themore » expression of platelet membrane glycoprotein IIb, protein tyrosine kinase, sialyltransferase, and Cu/ZnSOD was significantly greater after 3 days as a result of 1 Gy of whole body irradiation. Moreover, local irradiation to the thorax, abdomen, or left subphrenic area, which are frequently exposed to therapeutic radiation doses, showed a tendency toward radiation-induced increased expression of these genes in both the blood and the locally irradiated organs. Western blot analysis also corroborated these results. Conclusion: Platelet membrane glycoprotein IIb, protein tyrosine kinase, sialyltransferase, and Cu/ZnSOD might be candidates for biomarkers of radiation exposure. However, additional experiments are required to reveal the relationship between the expression levels and the prognostic effects after irradiation.« less
  • Mammary ductal cells are the origin for 70 to 80% of breast cancers. Nipple aspirate fluid (NAF) contains proteins directly secreted by the ductal and lobular epithelium in non-lactating women. Proteomic approaches offer a largely unbiased way to evaluate NAF as a source of biomarkers and are sufficiently sensitive for analysis of small NAF volumes (10 to 50 ml). In this study, we initially evaluated a new process for obtaining NAF and discovered that this process resulted in a volume of NAF that was suitable for analysis in ~90% of subjects. Proteomic characterization of NAF identified 64 proteins. Although thismore » list primarily includes abundant and moderately abundant NAF proteins, very few of these proteins have previously been reported in NAF. At least 15 of the NAF proteins identified have previously been reported to be altered in serum or tumor tissue from women with breast cancer, including cathepsin D and osteopontin. In summary, this study provides the first characterization of the NAF proteome and identifies several candidate proteins for future studies on breast cancer markers in NAF.« less