Enzymatic synthesis of uracil glucuronide, labeling with 125/131I, and in vitro evaluation on adenocarcinoma cells
Küçük Resim Yok
Tarih
2010
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
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 125/131I-UNG and 125/131I-UOG presented good incorporation ratios for Hutu-80, Caco-2, Detroit 562, and ACBRI 519 cells. The incorporation ratios of 125/131I-UOG were higher than those of 125/131I-UNG and of other labeled components for all cell types, and were also statistically significant compared to the values of 125/131I-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. © 2010, Mary Ann Liebert, Inc. 2010.
Açıklama
Anahtar Kelimeler
125I, 131I, adenocarcinoma cell lines, UDP glucuronidase, uracil glucuronide
Kaynak
Cancer Biotherapy and Radiopharmaceuticals
WoS Q Değeri
Scopus Q Değeri
Q2
Cilt
25
Sayı
3
