Enzymatic synthesis of uracil glucuronide, labeling with [sup.125/131]I, and in vitro evaluation on adenocarcinoma cells

Human UDP-glucuronosyltransferases (UGTs) are a family of membrane-bound enzymes of the endoplasmic reticulum. They catalyze the glucuronidation of various endogenous and exogenous compounds, converting them into more polar glucuronides. In this study, uracil glucuronide was enzymatically synthesize...

Full description

Saved in:
Bibliographic Details
Published inCancer biotherapy & radiopharmaceuticals Vol. 25; no. 3; p. 335
Main Authors Medine, Ilker Emin, Unak, Perihan, Sakarya, Serhan, Toksoz, Feriha
Format Journal Article
LanguageEnglish
Published Mary Ann Liebert, Inc 01.06.2010
Subjects
Adenocarcinoma
Cancer
Cancer cells
Care and treatment
Diagnosis
Enzymes
Monoclonal antibodies
Physiological aspects
Online AccessGet full text

Cover

More Information
Summary:Human UDP-glucuronosyltransferases (UGTs) are a family of membrane-bound enzymes of the endoplasmic reticulum. They catalyze the glucuronidation of various endogenous and exogenous compounds, converting them into more polar glucuronides. In this study, uracil glucuronide was enzymatically synthesized using a UGT-rich microsome preparate, which was separated from Hutu-80 cells. Two different glucuronide derivatives were obtained, with a total reaction yield of 22.95% ± 2.4% (n = 4). The glucuronide ligands were defined as uracil-n-glucuronide (UNG) and uracil-o-glucuronide (UOG). These were then analyzed by high-performance liquid chromatography-mass spectrometry and labeled with I-125 and I-131, separately. The radiolabeled [sup.125/131]I-UNG and [sup.125/131]I-UOG presented good incorporation ratios for Hutu-80, Caco-2, Detroit 562, and ACBRI 519 cells. The incorporation ratios of [sup.125/131]I-UOG were higher than those of [sup.125/131]I-UNG and of other labeled components for all cell types, and were also statistically significant compared to the values of [sup.125/131]I-UNG for primary human intestinal epithelial cells (ACBRI 519) and human intestinal adenocarcinoma cells. Cell incorporation rates of n-glucuronides and o-glucuronides were higher compared to uracil, with o-glucuronides being more selective. The results suggest that both I-125- and I-131-labeled glucuronides can be used in imaging and therapy, and further research should be done in preclinical stages. Key words: adenocarcinoma cell lines, [sup.125]I, [sup.131]I, UDP glucuronidase, uracil glucuronide
ISSN:1084-9785
1557-8852
DOI:10.1089/cbr.2009.0727