This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall goal of our research is to utilize carbon-14 labeled vitamin B12 (14C-B12) and accelerator mass spectrometry (AMS) to assess the absorption and turnover of vitamin B12 in humans, as well as the bioavailability of vitamin B12 from foods. With respect to absorption and turnover, we have dosed 6 healthy control subjects with 14C-B12 (50 nCi, 1.3 ?g) and collected baseline and post-dose blood, urine, and stool samples for assessment of 14C-B12 by AMS. The data show relatively consistent patterns of absorption and turnover among the subjects, including first appearance of 14C-B12 in the plasma at about 3 hours, peak plasma levels between 6 and 8 hours, followed by similar plasma elimination curves. A surprising finding has been our observation of high levels of 14C in the urine (30-40% of the administered dose), which is in direct contrast to previous literature reports of 0.1-0.5% of the administered dose in studies using 57Co-labeled vitamin B12. We have hypothesized that we are observing breakdown of the vitamin B12 in the gastrointestinal track that was not possible to observe when using 57Co-B12. This finding has potential implications for the bioavailability of B12 from pills and from foods to which vitamin B12 has been added as a fortificant. Future studies will focus on determining if 14C-B12 can be used to diagnose vitamin B12 malabsorption syndromes (e.g. pernicious anemia) and developing a model for vitamin B12 absorption and turnover in humans. In addition, we will attempt to determine how vitamin B12 is broken down in the gastrointestinal tract and what are the products of this breakdown that seem to be appearing in the urine.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR013461-13
Application #
8362757
Study Section
Special Emphasis Panel (ZRG1-BCMB-K (40))
Project Start
2011-06-01
Project End
2012-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
13
Fiscal Year
2011
Total Cost
$23,406
Indirect Cost
Name
Lawrence Livermore National Laboratory
Department
Biology
Type
Organized Research Units
DUNS #
827171463
City
Livermore
State
CA
Country
United States
Zip Code
94550
Wan, Debin; Yang, Jun; Barnych, Bogdan et al. (2017) A new sensitive LC/MS/MS analysis of vitamin D metabolites using a click derivatization reagent, 2-nitrosopyridine. J Lipid Res 58:798-808
Stornetta, Alessia; Zimmermann, Maike; Cimino, George D et al. (2017) DNA Adducts from Anticancer Drugs as Candidate Predictive Markers for Precision Medicine. Chem Res Toxicol 30:388-409
Wang, Si-Si; Zimmermann, Maike; Zhang, Hongyong et al. (2017) A diagnostic microdosing approach to investigate platinum sensitivity in non-small cell lung cancer. Int J Cancer 141:604-613
Wang, Zhican; Fang, Ying; Teague, Juli et al. (2017) In Vitro Metabolism of Oprozomib, an Oral Proteasome Inhibitor: Role of Epoxide Hydrolases and Cytochrome P450s. Drug Metab Dispos 45:712-720
Kim, Jeffrey; Stewart, Benjamin; Weiss, Robert H (2016) Extraction and Quantification of Tryptophan and Kynurenine from Cultured Cells and Media Using a High Performance Liquid Chromatography (HPLC) System Equipped with an Ultra-Sensitive Diode Array Detector. Bio Protoc 6:
Pan, Amy; Zhang, Hongyong; Li, Yuanpei et al. (2016) Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer. Nanotechnology 27:425103
Wang, Sisi; Zhang, Hongyong; Scharadin, Tiffany M et al. (2016) Molecular Dissection of Induced Platinum Resistance through Functional and Gene Expression Analysis in a Cell Culture Model of Bladder Cancer. PLoS One 11:e0146256
McCartt, A D; Ognibene, T; Bench, G et al. (2015) Measurements of Carbon-14 With Cavity Ring-Down Spectroscopy. Nucl Instrum Methods Phys Res B 361:277-280
Cai, Hong; Scott, Edwina; Kholghi, Abeer et al. (2015) Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice. Sci Transl Med 7:298ra117
Tomlinson, Ben; Lin, Tzu-yin; Dall'Era, Marc et al. (2015) Nanotechnology in bladder cancer: current state of development and clinical practice. Nanomedicine (Lond) 10:1189-201

Showing the most recent 10 out of 123 publications