The antibodies against 5-bromo-2′-deoxyuridine specifically recognize trifluridine incorporated into DNA

Hiroyuki Kitao, Yosuke Morodomi, Shinichiro Niimi, Mamoru Kiniwa, Kazuhiko Shigeno, Kazuaki Matsuoka, Yuki Kataoka, Makoto Iimori, Eriko Tokunaga, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara

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Abstract

Trifluridine (FTD) is a key component of the novel oral antitumor drug TAS-102 (also named TFTD), which consists of FTD and a thymidine phosphorylase inhibitor. FTD is supposed to exert its cytotoxicity via massive misincorporation into DNA, but the underlying mechanism of FTD incorporation into DNA and its correlation with cytotoxicity are not fully understood. The present study shows that several antibodies against 5-bromo-2′-deoxyuridine (BrdU) specifically cross-react with FTD, either anchored to bovine serum albumin or incorporated into DNA. These antibodies are useful for several biological applications, such as fluorescence-activated cell sorting, fluorescent immunostaining and immunogold detection for electron microscopy. These techniques confirmed that FTD is mainly incorporated in the nucleus during S phase in a concentration-dependent manner. In addition, FTD was also detected by immunohistochemical staining in paraffin-embedded HCT-116 xenograft tumors after intraperitoneal administration of FTD. Intriguingly, FTD was hardly detected in surrounding matrices, which consisted of fibroblasts with marginal expression of the nucleoside transporter genes SLC29A1 and SLC29A2. Thus, applications using anti-BrdU antibodies will provide powerful tools to unveil the underlying mechanism of FTD action and to predict or evaluate the efficacy and adverse effects of TAS-102 clinically.

Original languageEnglish
Article number25286
JournalScientific reports
Volume6
DOIs
Publication statusPublished - May 3 2016

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Trifluridine
Bromodeoxyuridine
Antibodies
DNA
Nucleoside Transport Proteins
Thymidine Phosphorylase
Bovine Serum Albumin
S Phase
Heterografts
Antineoplastic Agents
Paraffin
Electron Microscopy
Flow Cytometry
Fibroblasts
Staining and Labeling
Genes
Neoplasms
TAS 102

All Science Journal Classification (ASJC) codes

  • General

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The antibodies against 5-bromo-2′-deoxyuridine specifically recognize trifluridine incorporated into DNA. / Kitao, Hiroyuki; Morodomi, Yosuke; Niimi, Shinichiro; Kiniwa, Mamoru; Shigeno, Kazuhiko; Matsuoka, Kazuaki; Kataoka, Yuki; Iimori, Makoto; Tokunaga, Eriko; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko.

In: Scientific reports, Vol. 6, 25286, 03.05.2016.

Research output: Contribution to journalArticle

Kitao, H, Morodomi, Y, Niimi, S, Kiniwa, M, Shigeno, K, Matsuoka, K, Kataoka, Y, Iimori, M, Tokunaga, E, Saeki, H, Oki, E & Maehara, Y 2016, 'The antibodies against 5-bromo-2′-deoxyuridine specifically recognize trifluridine incorporated into DNA', Scientific reports, vol. 6, 25286. https://doi.org/10.1038/srep25286
Kitao, Hiroyuki ; Morodomi, Yosuke ; Niimi, Shinichiro ; Kiniwa, Mamoru ; Shigeno, Kazuhiko ; Matsuoka, Kazuaki ; Kataoka, Yuki ; Iimori, Makoto ; Tokunaga, Eriko ; Saeki, Hiroshi ; Oki, Eiji ; Maehara, Yoshihiko. / The antibodies against 5-bromo-2′-deoxyuridine specifically recognize trifluridine incorporated into DNA. In: Scientific reports. 2016 ; Vol. 6.
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