title: The antibodies against 5-bromo-2'-deoxyuridine specifically recognize trifluridine incorporated into DNA.
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.
authors.affiliation: Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.|Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Morodomi
authors.affiliation: Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.|Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan.|Taiho Pharmaceutical Co. Ltd., Tokushima 771-0194 and Ibaraki 300-2611, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Niimi
authors.affiliation: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan.|Taiho Pharmaceutical Co. Ltd., Tokushima 771-0194 and Ibaraki 300-2611, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kiniwa
authors.affiliation: Taiho Pharmaceutical Co. Ltd., Tokushima 771-0194 and Ibaraki 300-2611, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shigeno
authors.affiliation: Taiho Pharmaceutical Co. Ltd., Tokushima 771-0194 and Ibaraki 300-2611, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.|Taiho Pharmaceutical Co. Ltd., Tokushima 771-0194 and Ibaraki 300-2611, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Iimori
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Tokunaga
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.|Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001973:Bromodeoxyuridine / Q000276:immunology*; D045744:Cell Line, Tumor; D003584:Cytological Techniques / Q000379:methods; D004247:DNA / Q000737:chemistry*; D004195:Disease Models, Animal; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D009369:Neoplasms / Q000473:pathology; D014271:Trifluridine / Q000032:analysis*
chemical_list: D000906:Antibodies; D004247:DNA; D001973:Bromodeoxyuridine; D014271:Trifluridine