Repeated exposure to 5-bromo-2'-deoxyuridine causes decreased proliferation and low-grade inflammation in the lungs of mice.
Incorporation of 5-bromo-2'-deoxyuridine (BrdU) into proliferating cells has been used to label dividing cells in many tissues. Although BrdU has been shown to be genotoxic, teratogenic and mutagenic, such adverse effects have largely been ignored by researchers. We determined whether long-term BrdU exposure causes any histopathological changes in the lungs of mice. Eight-week-old male C57/BL6J mice were administered BrdU by intraperitoneal injection on 3 consecutive days of each week for 14 weeks. While no obvious structural changes such as tissue damage, fibrosis, emphysema, airway remodeling, vascular thickening or tumorigenesis were noted, a moderate degree of macrophage infiltration was observed in the airways and lung parenchyma in the lungs of the mice exposed repeatedly to BrdU (BrdU-exposed mice). The proliferative activities of the airway and alveolar epithelial and mesenchymal cells were reduced in the BrdU-exposed mice, although the numbers of these cells in the lungs were maintained. Double immunofluorescence study of the lungs of the BrdU-exposed mice showed overexpression of IL-6 in the airway epithelial and alveolar wall cells, some of which were also double-positive for BrdU. These results indicate that long-term exposure to BrdU inhibits cell proliferation and induces low-grade inflammation in the lungs of mice. Our findings underscore the need for caution in the interpretation of studies that involve long-term exposure to BrdU.
Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki 300-0395, Ibaraki, Japan.
Takao
T
Tsuji
Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki 300-0395, Ibaraki, Japan.
Masayuki
M
Itoh
Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki 300-0395, Ibaraki, Japan.
Ryota
R
Kikuchi
Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki 300-0395, Ibaraki, Japan.
Tomonori
T
Uruma
Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki 300-0395, Ibaraki, Japan.
Hidehiro
H
Watanabe
Comprehensive and Internal Medicine, Tokyo Women's Medical University Medical Center East, 2-1-10 Nishi-ogu, Arakawa-ku, Tokyo 116-8567, Japan.
Kazuhiro
K
Yamaguchi
Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki 300-0395, Ibaraki, Japan.
Hiroyuki
H
Nakamura
Department of Respiratory Medicine, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuou, Ami, Inashiki 300-0395, Ibaraki, Japan. Electronic address: kaoshiba@tokyo-med.ac.jp.
Kazutetsu
K
Aoshiba
D000818:Animals; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000187:drug effects; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects
D001973:Bromodeoxyuridine
Bromodeoxyuridine; DNA damage; Interleukin-6; Lung inflammation; Macrophage; Proliferation